tbuckley/cabot-search huggingface dataset:
Clinical parameters’ model for predicting distant metastasis (DM) following definitive therapy in patients with localized esophageal and esophagogastric junction (E-EGJ) cancer.
Authors: Kazuki Sudo, Xuemei Wang, Roopma Wadhwa, Hironori Shiozaki, Wayne Lewis Hofstetter, David C. Rice, Jeffrey H. Lee, Manoop S. Bhutani, Brian Weston, Heath D. Skinner, Ritsuko Komaki, Dipen M. Maru, Mariela A. Blum, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2014)

89 Background: For localized E-EGJ cancer patients, chemoradiation followed by surgery (trimodality therapy [TMT]) or definitive chemoradiation (bimodality therapy [BMT]) are considered the standard of care. However, ˜30-40 % of patients with localized E-EGJ cancer develop DM. We hypothesized that a clinical parameters’ model can be established to predict DM. Methods: We analyzed E-EGJ cancer patients who completed TMT or BMT from our prospectively maintained database. Logistic regression models were used for analysis. Overall survival (OS) was estimated by the Kaplan-Meier method. We used the AJCC 6th edition. Results: Between 2002 and 2013, 356 TMT patients and 273 BMT patients were analyzed. 33% (119/356) of TMT patients and 40% (109/273) of BMT developed DM as a first relapse. The median OS from DM were 10.2 months (95% CI: 7.8-12.7) for TMT patients and 7.8 months (95% CI: 5.7-9.9) for BMT patients. In a logistic regression analysis for all patients, the following parameters were associated with a significantly increased risk of DM: age (odds ratio [OR]: 0.97 [95% CI: 0.96-0.99]), initial standardized uptake value (iSUV) of PET (OR: 1.02 [95% CI: 1.00-1.04]), Stage III/IVa (vs. I/II) (OR: 2.43 [95% CI 1.65-3.57]) and male (vs. female) (OR 3.99 [95% CI: 1.89-8.42]). For TMT patients, baseline T3/T4 (vs. T1/T2) (OR 2.75 [95%CI 1.10-6.86]), baseline N1 (vs. N0) (OR: 1.69 [95% CI: 1.03-2.77]), and poorly differentiated cancer (vs. well/moderately differentiated) (OR 1.78 [95% CI: 1.13-2.82]) were significantly associated with DM. Conclusions: Our data suggest that younger men with Stage III/IVa cancer and high iSUV are at risk for DM irrespective of local therapy (TMT or BMT). A nomogram to predict DM will be developed with a larger cohort. Supported by UT M. D. Anderson Cancer Center Multidisciplinary Research Grants, CA138671, CA172741, CA129926 from NCI (JAA) and Generous Donors.
Circulating tumor cells (CTCs) in biochemical recurrence (BR) of prostate cancer: Final results.
Authors: Jeanny B. Aragon-Ching, Samuel J. Simmens, Ramez Andrawis, Frederick Hendricks, Harold Frazier, Michael Phillips, Thomas Jarrett, Steven R. Patierno, Robert S. Siegel
Journal: Journal of Clinical Oncology (2013)

179 Background: CTCs have known prognostic implications in metastatic prostate cancer. We presented initial data on the role of CTCs in BR of prostate cancer (Aragon-Ching et. al., ASCO GU 2011). The primary aim of this study was to determine whether there is a correlation between the number of CTCs with prostate specific antigen (PSA) levels and PSA doubling time (PSADT) in men with BR. Methods: BR was defined as patients who have undergone primary treatment with prostatectomy or radiation or both, with a rise to ≥ 0.2 from a prior undetectable level for prior prostatectomy or &gt; 2 mg/dl rise for post-nadir radiotherapy. 36 patients (pts) were enrolled from May 2010 to May 2012. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. Results: The median age for 36 pts was 69.5 (range: 51 – 91) with a median PSA of 1.65 ng/mL (range 0.2 – 65.8) and testosterone levels of 315 ng/dL (range: 31 – 727). Gleason scores ranged from 5 to 9 (median=7). Prostatectomy was the primary treatment in 25 pts, radiotherapy in 9 pts, Cyberknife in 1 pt and combined radiohormones in 1 pt. PSADT varied between 0.35 to 55 months, with a median of 7.43 mos. The incidence of positive CTCs was 8.3% (3 out of 36 pts) of whom 2 had biopsy-proven bony lesions upon presenting with equivocal scans. The 3 pts who had measurable CTCs had PSADT of 2.27, 4.99 and 3.08 months, respectively. Conclusions: Obtaining CTCs in unselected patients presenting with biochemical recurrence have low yield. However, obtaining a positive CTC raises the suspicion of presence of metastatic disease and may have utility for longitudinal follow-ups of patients with BR. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute.
Pharmacokinetic and pharmacodynamic analysis of gastric cancer patients treated with telatinib.
Authors: A. Burd, J. Castillo, M. Whiteside, M. White, J. A. Ajani, A. Fattaey, L. A. Kunkel
Journal: Journal of Clinical Oncology (2011)

113 Background: The soluble form of the VEGFR2 receptor (sVEGFR2) neutralizes circulating VEGF, and functions as a negative feedback mechanism to enable partial inhibition of VEGF-stimulated endothelial cell migration and proliferation. In response to inhibition of VEGFR2 tyrosine kinase activity, up-regulation of VEGF expression and down-regulation of sVEGFR2 expression levels have been observed (Murukesh et al., 2010). Telatinib (tel) is a novel orally available kinase inhibitor that is highly selective for the VEGFR, PDGFR, and KIT tyrosine kinases at nanomolar concentrations with potent antiangiogenic activity. Correlation between telatinib exposure and reduction in plasma sVEGFR2 levels from baseline has previously been demonstrated in patient serum samples in phase I studies. Methods: TEL0805, a phase II study administered tel with capecitabine (X) and cisplatin (P) in previously untreated metastatic or unresectable gastric or GEJ adenocarcinoma pts. Patient serum samples were obtained on day -7, [6 plasma samples (pre-dose, and at 30 min, 1, 2, 3 and 4 hours)] and on day 1, [4 plasma samples (pre-dose and at 1, 2 and 3 hours)] and evaluated for the levels of telatinib and its M2 metabolite (M2). Additional serum samples were collected every 42 days and evaluated for VEGF and sVEGFR2 levels. Results: Measurement of tel and M2 levels confirmed previous pharmacokinetic findings and demonstrated no drug accumulation following continuous daily dosing. Baseline plasma sVEGFR2 levels have previously not been reported for advanced gastric cancer patients and displayed a wide range at disease presentation. Reduction in sVEGFR2 levels were noted for nearly all treated patients and correlated with the duration of stay on tel therapy. Conclusions: Telatinib continuous dosing is possible in combination with XP with little effect on tel exposure or accumulation. Reduction in sVEGFR2 levels may be useful in identifying patients who may benefit from tel treatment in this combination setting. [Table: see text]
Perspectives of patients with colorectal cancer (PCRC): A pilot project to determine interests in and understanding of patient education on clinical research
Authors: N. Love, A. Grothey, S. Curley, L. Ellis, H.-J. Lenz, M. Paley, R. Kaderman, K. Ziel, D. Paley
Journal: Journal of Clinical Oncology (2005)

3635 Background: Our previous needs assessments in patients with breast and prostate cancer documented considerable interest in obtaining more information on clinical trial results and participation. This pilot project launched a parallel effort in PCRC. Methods: PCRC attended a daylong meeting in Nov 2004 in which a physician moderator queried a research leader panel in an informal interactive format. Attendees were anonymously polled for feedback. Results: 42 PCRC and 30 guests attended. PCRC demographics: Median time from diagnosis: 3–5 yrs, 35% with metastatic disease: 66% treated at a cancer center. Prior therapies: surgery, 93%; chemotherapy, 83%; radiation therapy, 53%. Attendees highly rated the discussion on different topics for their interest and comprehension (Table). The information also had relevance for clinical decision-making. After the discussion, 41% reported a change in their perspective on laparoscopic surgery; 93% now preferred open surgery. After the panel discussed the rationale and risks of adjuvant chemotherapy (AC), attendees were asked what AC they would prefer for a stage III tumor. 57% chose FOLFOX: 23% a 5-FU regimen. In considering the risk-benefit ratio of FOLFOX, 54% would be treated for a 1–5% absolute benefit in 5-yr survival but 24% required more than a 20% benefit. While 70% of PCRC were not offered clinical trial participation, 52% would participate in a randomized adjuvant trial of FOLFOX ± bevacizumab. Conclusions: This format was generally well-received, well-understood, and relevant to clinical decision-making. The next step in this initiative is to investigate more efficient mechanisms to deliver research leader perspectives. We plan to recruit 150 PCRC for a telephone survey, which will include audio excerpts from the meeting, querying patients about the potential value of this and related content, and delivery methods, including downloadable audio. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron, Genentech, ImClone Systems, Response Genetics, Sanofi-Synthelabo Genentech, Lilly Oncology, Novartis, Pfizer, Roche, Sanofi, Sanofi-Synthelabo ImClone Systems, NCI, NIH
Cancer treatment side effects in breast cancer patients receiving radiation therapy
Authors: M. Hofman, J. T. Hickok, G. R. Morrow, J. A. Roscoe, L. J. Gillies, S. L. Ranson
Journal: Journal of Clinical Oncology (2005)

705 Background: A main goal of cancer research is to reduce the suffering of cancer patients, which exhibits itself in many ways, e.g. a reduction in the quality of life (QOL) and/or activity, the ability to work or even walk; problems in relationships; and changes in mood among many others. This study investigated side effects that breast cancer patients experience during their radiation treatment. Methods: Breast cancer patients (n=218) receiving radiation treatment at the James P. Wilmot Cancer Center in Rochester, New York during 2003 were surveyed weekly regarding 12 common side effects. Patients rated symptom severity using an 11-point Likert scale, from 0 ("Not Present") to 10 ("As Bad As You Can Imagine"). They also rated the effect of the 12 symptoms, on work, activity, QOL, mood, walking, and relationships on similar 11-point scales. Results: Using any non-zero value at any time during treatment to indicate the presence of the symptom, fatigue was the most commonly reported side effect with 84% of patients reporting it; nausea (25%) and vomiting (9%) were two of the least common. Seven of the 12 symptoms were experienced by more than 50% of patients. 70% of patients reported that side effects affected their ability to work. The proportion of patients experiencing the other 11 side effects and the impact of symptoms on other aspects of patients' lives are shown in the table. Both stepwise linear regression and exhaustive chaid analyses showed that changes in pain intensity over time had the greatest influence on patients' lives. Conclusions: Breast cancer patients undergoing radiation therapy are suffering from a large number of side effects, which adversely affect their QOL, activities, work, moods and relationships. No significant financial relationships to disclose.
Intratumor heterogeneity of DNA copy number aberrations in gastric and oesophageal adenocarcinomas.
Authors: Matthew N Davies, Donat Alpar, Beatrice Griffiths, Louise J Barber, Kamil A Lipinski, Zakaria Eltahir, Emese Agoston, Laszlo Harsanyi, Andrew Wotherspoon, A Marcell Szasz, Marco Gerlinger
Journal: Journal of Clinical Oncology (2015)

78 Background: DNA copy number aberrations (CNAs) are common in oesophageal and gastric adenocarcinomas (OGCs) and display extensive inter-tumour heterogeneity. CNA patterns define gastric cancer molecular subtypes and ERBB2 amplifications, present in a small fraction of patients with OGC, are predictive for ERBB2-targeted drug sensitivity. Together, this suggests a critical role of CNAs determining OGC tumour biology and clinical outcomes. Despite this, predictive and prognostic CNA biomarkers have not been identified for the majority of OGCs, precluding the development of effective personalized therapy approaches for these aggressive tumours. Intra-tumour heterogeneity, characterized by the presence of multiple subclones with distinct genetic profiles within an individual cancer, can hinder the accurate molecular analysis and classification of tumours. The aim of this pilot study was to assess whether chemotherapy-naïve localized OGCs display intra-tumour macroheterogeneity of CNA profiles. Methods: Tissue specimens from four tumour regions representing the macroscopic spatial extent of each of five OGCs were systematically collected after surgical resection. DNA extracted from these FFPE specimens was analysed by molecular inversion probe SNP arrays for high resolution CNA detection. Results: Comparison of genome wide copy number and B-allele frequency profiles suggested highly concordant CNA profiles across the regions from individual primary tumours. Eight driver CNAs leading to amplification of the MET, KRAS, ERBB2, PIK3CA or FGFR2 oncogenes were identified in 4/5 tumours. Only one out of these eight driver CNA’s, harbouring the KRAS oncogene, was heterogeneous within a tumour. Conclusions: Although chromosomal instability is thought to be common in this tumour type, this pilot study suggests that macroheterogeneity is limited and that CNA profiles assessed from a single tumour biopsy are likely to be representative of the dominant CNA profile of localized OGCs. Thus, clinical correlative CNA analyses may be possible from single biopsies of localized OGCs. Mutational heterogeneity and microheterogeneity in microdissected and single cells are currently being investigated.
A phase I trial of recombinant modified vaccinia ankara (MVA) vaccine encoding Epstein-Barr virus (EBV) antigens.
Authors: E. P. Hui, G. S. Taylor, B. Ma, S. L. Chan, R. Ho, W. Wong, H. Jia, C. Edwards, A. B. Rickinson, A. T. C. Chan, N. M. Steven
Journal: Journal of Clinical Oncology (2011)

2592 Background: EBV+ve nasopharyngeal carcinoma (NPC) selectively expresses the EBV-coded nuclear antigen EBNA1 and latent membrane protein LMP2. A recombinant vaccinia virus MVA-EL, encodes an EBNA1/LMP2 fusion, is designed to boost T cell immunity to these tumour-associated antigens. It was tested in Hong Kong, an area endemic for NPC, in a phase I dose escalation trial to determine a safe and immunogenic dose for phase II. Methods: MHC I/II-typed NPC patients (pts), all >12 weeks after primary therapy, received three intra-dermal vaccinations of MVA-EL at 3-weekly intervals, with dose escalations of 5x107, 1x108, 2x108, 3.3x108 and 5x108 pfu providing dose limiting toxicity (DLT) had not been observed on the previous cohort. Blood samples were taken during pre-screening, immediately before and 1 week after each cycle of vaccination, and at 11, 14, 26 and 52 weeks post-vaccination. Cryo-preserved peripheral blood mononuclear cells (PBMC) were later tested for spot-forming cells (sfc) in interferon-gamma ELIspot assays against complete EBNA1 and LMP2 15-mer peptide mixes and against defined epitope peptides selected according to MHC-type. Results: Eighteen pts were treated, three per dose level 1-4 and six at the highest dose. No DLT occurred. Pre-existing immunity to EBNA1 and/or LMP2 was observed in 16/18 pts with mean frequencies of 181 (EBNA1) and 81 (LMP2) sfc/106 PBMC. Immunity to one or both antigens was significantly increased in 15/18 pts, with mean sfc/106 PBMC among responders reaching 411 and 237 after the second, and 353 and 213 after the third vaccination, while immunity to control antigens (a non-vaccine EBV antigen and influenza) showed no such change. Furthermore, the size of EBNA1/LMP2 responses strongly suggested a linear relationship with vaccine dose. Screening on defined peptides identified individuals mounting both MHC I and II-restricted responses to known epitopes in one or both target antigens. Conclusions: MVA-EL is safe and immunogenic at all doses tested. The recommended dose for phase II is 5x108pfu because this dose induced the strongest responses. Acknowledgement: Supported by Cancer Research UK, Research Grant Council of Hong Kong (CUHK 460708) and Hong Kong Cancer Fund.
Hollow spheroids beyond the invasive front and malignant potential of colorectal cancer.
Authors: Shozo Yokoyama, Junji Ieda, Naoyuki Yamamoto, Yasuyuki Mitani, Yuki Mizumoto, Katsunari Takifuji, Tsukasa Hotta, Kenji Matsuda, Takashi Watanabe, Masaji Tani, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2014)

418 Background: Hollow spheroid (HS) is a morophogenesis after budding at invasion front of colorectal cancer (CRC) tissue. HS formation of CRC cells has been shown to be induced by Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1) long cytoplasmic isoform dominance condition in three-dimensional (3D) in vitro culture. The aim of the current study is to address the existence and the clinical implication of HS in colorectal cancer. Methods: Immunohistochemical analyses were conducted with CEACAM1, CEACAM1-L, to address the existence of CEACAM1 expressing HS beyond the invasion front of CRC. The risk factors for metastases and survival were calculated using univariate and multivariate analyses on clinical samples from 164 patients with CRC. To investigate the role of HS for chemoresistance to 5-fluorouracil (5-FU), the risk factors for recurrence after adjuvant chemotherapy were calculated using univariate and multivariate analyses on clinical samples from 82 patients with Stage III CRC. Results: Immunohistochemical analyses showed that CEACAM1 expressing HS existed at the invasion front of colorectal cancer tissues. A multivariate analysis showed that the HS is an independent risk factor for lymph node metastasis (p = 0.004) and distant metastasis (p = 0.002). HS was also identified to be an independent prognostic factor by a Cox proportional hazards model (p = 0.020). The Kaplan-Meier evaluation for the overall survival analysis showed that HS was significantly associated with a shorter survival (p &lt; 0.0001). Moreover, a multivariate analysis for recurrence after adjuvant chemotherapy showed that the HS is an independent risk factor (p = 0.0079). These results suggested that HS indicates malignant and chemoresistant phenotype. Conclusions: HS was significantly correlated with CRC metastasis, poor survival and chemoresistance to 5-FU. HS beyond the invasion front of CRC can be useful for diagnosis of malignant potential, and may be novel therapeutic target.
Evaluation of temozolomide (TMZ) activity in a mouse model of brain metastases (BM) from breast cancer (BC)
Authors: M. Romani, M. Cilli, C. Neumaier, G. Baio, F. Piccardi
Journal: Journal of Clinical Oncology (2008)

12014 Background: Cerebral metastases are observed in ∼15% of BC patients within 2 years from diagnosis. Recently, there has been an increase in the incidence of BM, likely due to increased survival achieved with novel therapies. Overexpression of HER2 is a significant risk factors associated with BM that cannot be efficiently controlled by trastuzumab. The objective of this study was to develop a mouse model of BC BM, in order to evaluate the efficacy of TMZ in controlling development & growth of the metastases. Methods: We developed an in vivo model, a MCF7 BC cell line (stably transfected with a luciferase reporter vector), intracranially injected at day 0 in immunodeficient mice. There were 3 groups of mice. Group 1 (n=5) no treatment; Group 2 (n=6) was treated with oral TMZ, 150 mg/m2 body surface, day 1–7; Group 3 (n=6) the same treatment, day 8- 14. All animals were sacrificed at day 30. Tumor growth was monitored by bio imaging (Xenogen Ivis 200) and by NMR. Histopathologic analysis was performed on brain tissue that had positive tumor growth (by NMR). Results: Bio-imaging showed a dramatic difference between the light intensity of control & of treated mice. Although the signal decreased over time in all groups, the median photon flux for both groups of treated mice was considerably lower than that of the control set. The decrease in signal intensity was more evident in Group 2 as compared to Group 3, although after 3 weeks the difference between the 2 treatment arms leveled off. At the end of the observation period, the photon flux of the mice in group 2 and 3 were respectively 8.48 and 6.54 fold lower than that of the control mice. NMR imaging confirmed the tumor growth observed by bio-imaging. Conclusions: Results indicate that, with time, the majority of injected cells die and this occurs more rapidly in treated animals as compared to controls. This suggests that TMZ may accelerate the elimination of free/ micro-clusters of cells, which could correspond to micrometastases, and also appear to reduce tumor load in this mouse model of BM from BC. No significant financial relationships to disclose.
Epoetin alfa (EPO) vs standard of care (SOC) decreases number of PRBC transfusions (tx) in patients (pts) receiving hyper-CVAD for acute lymphocytic leukemia (ALL), lymphoblastic lymphoma (LL), and Burkitt’s lymphoma (BL)
Authors: G. N. Mattiuzzi, H. Kantarjian, J. Cortes, M. Foudray, B. N. Bekele, D. Thomas, M. Cabanillas
Journal: Journal of Clinical Oncology (2005)

6703 Background: Anemia is common in ALL, LL, and BL on chemotherapy (chemo) and is associated with poor cancer control. Studies have shown that even mild correction of anemia has been associated with a significant improvement in quality of life (QOL). The current treatment for anemia in ALL, LL, and BL is PRBC tx. However, tx are time consuming and carry risk of infection and tx reaction. There are at least 2 studies that suggest EPO use may impair disease control. Objectives: To evaluate if EPO 1) decreases number of tx, 2) improves QOL, and 3) adversely influences CR rate. Methods: Pts with newly diagnosed ALL, LL, or BL, receiving hyper-CVAD were randomized to EPO vs. SOC within 14 days of starting chemo. EPO dose was 40,000 units SQ weekly and escalated to 60,000 units after 4 weeks if indicated. Both arms received blood tx as per guidelines. Pts filled out 2 QOL questionnaires (Anderson Symptom Assessment Score (ASAS) and FACT-Anemia) within one week of each chemo course. Results: From September 2003 to November 2004, 30 pts were enrolled. The 2 groups were comparable in baseline characteristics (sex, diagnosis, baseline hemoglobin, number of courses, and weeks on study), but EPO treated pts had a tendency to be younger than SOC pts (34 vs 48, respectively (p=0.028)). The median number of tx after the first 4 weeks on study, was 13 in SOC and 7.5 for EPO arm (p=0.14). All patients achieved CR. ASAS scores for fatigue improved by a mean score of +3.75 in EPO arm vs +0.25 for SOC when baseline and course 3 scores were compared (p=0.049). FACT-Anemia scores improved from baseline in both groups when compared to course 3. This improvement was more evident in the EPO group for patients who had a baseline hemoglobin of 9 or greater (EPO +27 SOC +18 p=0.7128)). Conclusions: 1) In pts with ALL, LL, and BL on hyper-CVAD, EPO decreased the number of tx. 2) Pts treated with EPO report significant improvements in fatigue symptoms. 3) Use of EPO appears to have no impact on CR rate. No significant financial relationships to disclose.