tbuckley/cabot-search huggingface dataset:
Phase II study of gefitinib and docetaxel for patients (pts) with advanced pancreatic adenocarcinoma (APC) progressing after first-line therapy. Final results
Authors: J. M. Brell, K. Matin, T. Evans, R. L. Volkin, G. J. Keifer, J. J. Schlesselman, S. Dranko, L. Rath, A. Schmotzer, R. K. Ramanathan
Journal: Journal of Clinical Oncology (2007)

4586 Background: Gemcitabine is the standard-of-care for APC; the epidermal growth factor receptor (EGFR) inhibitor erlotinib is sometimes added to initial therapy. Pre-clinical data supports the addition of the EGFR inhibitor gefitinib to docetaxel, an agent with activity in APC. Because there is no standard treatment after gemcitabine failure, this combination was examined in a phase II study. Methods: Pts were required to have APC and have failed one prior treatment regimen; EGFR over-expression was not required. The initial docetaxel dose was 75 mg/m 2 on day one every 21 days . Due to febrile neutropenia in 8 of 18 pts, the dose was reduced to 60 mg/m 2 . Gefitinib 250 mg/day orally was given continuously. Accrual of 41 pts was planned in a one-stage design to identify a targeted 50% improvement in median survival from 3.5 to 5.3 months (mo) by one-sided log-rank test (80% power, a = 0.05). Results: Forty five pts met eligibility and signed consent; 41 pts received treatment and were evaluable. Pt characteristics: 68% male, median age 63 yrs. (range 47 - 82). ECOG performance status (PS) 0 - 1 in all pts, except for 3 with PS of 2. Common treatment-related Grade 3 - 4 toxicities were: febrile neutropenia / infection in 11 pts (27%), with most events occurring at docetaxel dose of 75 mg/ m 2 (8 of 18 pts); fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). Only 3 pts discontinued treatment due to toxicities and more than 2 cycles were administered to 40% of patients. The median survival was 4.7 mo (95% CI 2.9 - 5.7 mo). Time to progression was 1.8 months. There was one partial response (PR) and stable disease (SD) in 14 pts. Conclusion: The combination of gefitinib (250 mg/d) and docetaxel (60 mg/ m 2 ) had evidence of some efficacy with one PR and SD in 14 pts. The median survival was 4.7 mo, somewhat lower than our intended target (5.3 mo). The tolerability and feasibility of second-line therapy for APC was demonstrated, and results of this study can be used as a benchmark to evaluate novel therapies in subsequent studies. (Supported by Astra Zeneca Pharmaceuticals) No significant financial relationships to disclose.
Effect of timing of information on exercise on exercise behavior during cancer treatment: A URCC CCOP protocol.
Authors: L. Sprod, L. J. Peppone, O. Palesh, M. C. Janelsins, C. E. Heckler, L. K. Colman, J. J. Kirshner, P. W. Bushunow, G. R. Morrow, K. M. Mustian
Journal: Journal of Clinical Oncology (2010)

9138 Background: Exercise may reduce many side effects of cancer treatment. However, determining the ideal time to provide cancer patients with information to promote exercise during treatment is necessary. Methods: A nationwide sample of newly diagnosed cancer patients who received chemotherapy and/or radiation completed an information needs assessment (INA) within 2 wks prior to beginning treatment (T1) and within 2 wks of treatment completion (T2). The INA included questions concerning the availability of information about using exercise during treatment and if available, whether that information was used. At T2 patients reported use of exercise since cancer diagnosis. Logistic regression was used to obtain odds ratios with 95% CI. Results: 748 patients were accrued (64% female, mean age=61 years, 47% breast cancer). At T1, 8 patients (1.5%) reported not being able to find information about exercise and 513 (98.5%) reported information was available. Of the 513, 375 (72%) reported using the information. At T2, 12 patients (2.5%) reported not being able to find information about exercise and 474 (97.5%) reported information was available. Of the 474, 345 (72.8%) reported using the information. Controlling for age, gender, cancer and treatment type, patients who were able to find information about exercise at T1 were more likely to exercise during treatment (OR=1.52; 95% CI=1.12-2.07; p=.007), and if patients were able to find information about exercise and use it, they were even more likely to exercise during treatment (OR=4.31; 95% CI=2.64-7.04; p<.001). Controlling for age, gender, cancer and treatment type, patients who were able to find information about exercise during their treatment, assessed at T2, were more likely to exercise during treatment (OR=2.55; 95% CI=1.84-3.52; p<.001), and if patients were able to find information about exercise and use it, they were even more likely to exercise during treatment (OR=5.92; 95% CI=3.74-9.35; p<.001). Conclusions: Cancer patients who were provided with information about exercise during treatment rather than within the 2 wks prior to treatment were more likely to participate in exercise during treatment. Funding: NCIR25CA10618 and U10CA37420. No significant financial relationships to disclose.
Prevalence and prognostic significance of myeloid-derived suppressor cells and regulatory T cells in pancreatic and esophagogastric cancer.
Authors: R. F. Gabitass, N. E. Annels, H. S. Pandha, G. W. Middleton
Journal: Journal of Clinical Oncology (2010)

e21006 Background: Myeloid derived suppressor cell (MDSC) and regulatory T cell (Treg) accumulation in cancer patients is proposed as an important mechanism of tumor immune evasion. We present for the first-time analysis of both MDSCs and Tregs in pancreatic and esophago-gastric cancer. Methods: Peripheral blood samples were collected from 35 pancreatic, 46 esophageal and 19 gastric cancer patients and 31 normal healthy volunteers. PBMC was harvested and stored in liquid N2 with subsequent flow cytometric analysis of MDSC (HLADR- Lin1- CD33+ CD11b+) and Treg (CD4+ CD25+ CD127low/- FoxP3+). Unpaired T tests were applied to analyse MDSC and Treg levels between groups. Kaplan-Meier survival analysis was performed to compare patients with normal MDSC levels (as defined by the controls range, 0%-2% total PBMCs) and high MDSCs (> 2%). Results: The mean percentage of MDSCs in each cancer group was significantly higher than controls; pancreatic 2.455% (p = 0.0005), esophageal 1.623% (p = 0.0260) and gastric 2.029% (p = 0.0326), with controls 1.104%. Pancreatic and esophago-gastric cancer patients had significantly higher mean Treg percentages than controls, p = 0.0036 and p = 0.0189 respectively. There was a significant positive correlation between upper GI cancer patients' MDSC and Treg scores (Spearman's rho +0.285; p = 0.008). Patients with normal MDSC levels survived longer than those with high levels (log rank: p = 0.011), median survival 231 vs. 145 days. The influence of MDSC score was further quantified by Cox regression analysis with MDSC score as a covariate: p < 0.0005. Treg percentage was not significantly associated with survival. Conclusions: Pancreatic and esophago-gastric cancer patients have elevated MDSC correlating with poor prognosis, indicating MDSCs as a potential biomarker for survival. We will present this data with further analysis of the longitudinal impact of chemotherapy and immunotherapy on number and function of MDSCs and Tregs in order to assess the augmentation by chemotherapy of responses to immunotherapy. No significant financial relationships to disclose.
Impact of adjuvant radiation therapy (RT) on recurrence and survival outcomes in stage IB-IIA endometrial cancer (EMCA) patients with lymph vascular invasion (LVSI)
Authors: F. Simpkins, C. Kunos, A. Mariani, J. Bakkum-Gamez, L. Landrum, K. Moore, C. Michener, P. G. Rose
Journal: Journal of Clinical Oncology (2008)

5568 Background: To determine the clinical outcomes of Stage IB-IIA EMCA patients (pts) with LVSI treated with and without adjuvant RT. Methods: We conducted a four-center retrospective study of pts with Stage IB-IIA EMCA who had LVSI. Papillary serous, clear cell histologies, and pts treated with chemotherapy were excluded. Comprehensive staging was not required. Pts were either observed (Obs), received vaginal brachytherapy (Brachy) or external beam therapy ± brachy (EBRT ± B). Results: We identified 128 pts (49 Obs, 30 Brachy, 49 EBRT ± B). 80 pts (62.5%) underwent surgical staging. Median age was 67 yrs and median follow-up was 5.3 yrs. We observed 32 total relapses, 14/49 (28%) in the Obs group, 2/30 (7%) in the Brachy and 16/49 (33%) in the EBRT ± B group. Relapse rates (RR) were similar between staged and unstaged pts. Of Obs pts, 79% of relapses occurred at the vagina. However, relapses occurred distantly in 100% of Brachy and 87.5% of EBRT ± B pts (p=0.11; p=0.014). For grade 1,2 and 3 tumors, RR were 4/28 (14%), 12/54 (22%), and 16/46 (35%) (p>0.05). In grade 1 and 2 tumors, relapse was 70% local and 31% distal whereas the majority of relapses for grade 3 were distal (88%) p<0.001. RR were significantly associated with tumor invasion of the lower uterine segment (LUS) p=0.035. Overall survival (OS) and cancer-related survival were not significantly impacted by adjuvant RT, due to distant failures. However, adjuvant RT improved pelvic control p=0.007. In a multivariate analysis, LUS invasion correlated with OS (p=0.008) while stage, age, tumor grade, myometrial invasion, and RT (p>0.06) were not. Conclusion: Overall RR for stage IB-IIA EMCA pts with LVSI are high (25%). Although adjuvant RT improved pelvic control, it did not impact RR, cancer-related or OS, likely secondary to distant failures. The role of systemic therapy ± RT for early stage EMCA with LVSI should be evaluated, particularly in pts with high grade tumors or involvement of the LUS. Table 1: Relapse rates for Stage Ib-IIa LVS+endometrial cancers Staged (n=80) Unstaged (n=48) Obs n=28 Brachy n=23 EBRT± B n=29 Obs n=21 Brachy n=7 EBRT± B n=20 Stage IB Total 0/3 (0%) 2/14 (14%) 1/8 (13%) 1/12 (8%) 0/4 (0%) 1/6 (17%) Vagina 0 0 0 1 0 1 Pelvic 0 0 0 0 0 0 Distal 0 2 1 0 0 0 Stage IC Total 8/20(40%) 0/6 (0%) 7/15 (47%) 1/6 (17%) 0/2 (0%) 3/12 (25%) Vagina 5 0 1 1 0 0 Pelvic 0 0 0 0 0 0 Distal 3 0 6 0 0 3 Stage IIA Total 1/5 (20%) 0/3 (0%) 3/6 (50%) 3/3(100%) 0/1 (0%) 1/2 (50%) Vagina 1 0 0 3 0 0 Pelvic 0 0 0 0 0 0 Distal 0 0 3 0 0 1 Total Recurrence Total 9/28(32%) 2/23 (9%) 11/29 (38%) 5/21(24%) 0/7 (0%) 5/20 (25%) Vagina 6/9 (67%) 0 1/11 (9%) 5/5(100%) 0 1/5 (20%) Pelvic 0 0 0 0 0 0 Distal 3/9 (33%) 2/2 (100%) 10/11 (91%) 0 0 4/5 (80%) Overall 22/80 (27%) Overall 10/48 (21%) No significant financial relationships to disclose.
The utility of an investigational real-time RT-PCR assay system for the detection of micrometastases in sentinel lymph nodes of breast cancer confirmed by 0.2 mm histological interval analysis
Authors: M. Kurozumi, Y. Kobayashi, H. Takei, K. Kitsugi, M. Ueno, R. Nishiguchi, G. Green, J. Vargo
Journal: Journal of Clinical Oncology (2007)

10560 Background: Comparison between real-time RT-PCR and histological analysis for the detection of lymph node metastasis in breast cancer patients is difficult because of the necessary use of different tissue for the two tests. In order to minimize this challenge this study used histology sections taken every 0.2 mm and all tissue between the sections was analyzed by real-time RT-PCR. Methods: 129 Lymph nodes (LNs) were obtained by Sentinel LN biopsy and/or axillary dissection from 80 breast cancer patients. All LNs were cut in half. One half of each LN was used for the routine intra-operative diagnosis. The other half was used for the 0.2mm histological interval analysis. All 10μm sections cut for histology at 0.2 mm intervals were analyzed using frozen section H&amp;E under a light microscope. All remaining tissue between the sections used for histological analysis was assayed by real-time RT-PCR using the genetic markers mammaglobin and cytokeratin-19 (investigational GeneSearch Breast Lymph Node Assay, Veridex, LLC, Warren, NJ, USA). Cutoffs were pre- set for the real-time RT-PCR to detect only metastasis greater than 0.2 mm. Results: Compared to the histological diagnosis using 0.2 mm interval frozen sections, the real-time RT-PCR results were as follows; sensitivity of 100.0% (34/34), specificity of 93.7% (89/95) and overall accuracy of 95.3% (123/129). Conclusions: These data suggest by utilizing the 0.2 mm histological interval analysis, sampling discrepancies are minimized and a high level of sensitivity and overall accuracy is seen for the real-time RT-PCR assay. Assay specificity calculations may be less than 100% due to interpretation challenges in frozen section histology, especially in the cases of smaller metastases and/or lobular cancer, causing a small percentage of clinically relevant metastasis to be missed. [Table: see text]
Prospective comparison of postoperative quality of life (QOL) in patients undergoing lobectomy by video-assisted thoracic surgery (VATS) versus thoracotomy for non-small cell lung cancer (NSCLC)
Authors: B. J. Park, N. M. Ishill, R. M. Flores, C. T. Gawiak, R. Shen, N. Rizk, M. S. Bains, R. J. Downey, J. Ostroff, J. Burkhalter, V. W. Rusch
Journal: Journal of Clinical Oncology (2008)

7543 Background: VATS lobectomy in early stage NSCLC is thought to have benefits over thoracotomy with regard to postoperative recovery and QOL, but prospective comparative data is lacking. Methods: A prospective, non-randomized trial was performed comparing postoperative QOL in patients undergoing lobectomy for pathologic stage I NSCLC either by VATS or thoracotomy. Validated patient-reported measures were administered pre- and postoperatively. Comparison of categorical variables was done by Fisher’s exact test, continuous data by Wilcoxon’s test, and QOL differences using ANOVA models adjusting for stage and baseline scores. Results: There were 129 eligible patients (62 thoracotomy, 67 VATS). There were no differences between groups with respect to gender distribution, age, preoperative lung function, or tumor size. There was a greater proportion of pathologic stage IB disease (53% versus 19%, p<0.01) in the thoracotomy group. There were no operative mortalities in either group. VATS patients had a shorter median length of hospital stay (4 days, range 2–18 versus 6 days, range 3–27, p=0.002). At a median follow-up of 23 days (range 11–34) after discharge use of VATS resulted in a higher proportion of patients with postoperative patient-reported Karnofsky performance status ≥90 compared to thoracotomy (68% versus 38%, p=0.02). In addition, VATS patients had improved outcomes with respect to dyspnea, fatigue and pain relative to baseline (Table). There were no differences in activities of daily living or global QOL as measured by MOS SF-36. Conclusions: VATS for lobectomy in early stage NSCLC resulted in shorter length of stay and significant improvements in immediate postoperative performance status, dyspnea, fatigue and pain compared with thoracotomy. Quality of Life Outcomes Characteristic Thoracotomy Baseline Thoracotomy Postoperative VATS Baseline VATS Postoperative p-value Baseline Dyspnea Index 4.8 ± 1.8 7.6 ± 2.1 4.7 ± 1.7 6.3 ± 1.9 0.002 Brief Fatigue Inventory 19.9 ± 21.9 38.3 ± 21.5 11.4 ± 15.7 24.8 ± 20.3 <0.0001 Brief Pain Inventory (BPI)-Severity 0.93 ± 1.4 2.8 ± 2.1 0.59 ± 1.3 1.6 ± 1.8 0.001 BPI-Interference 0.80 ± 1.6 2.8 ± 2.2 0.51 ± 1.0 1.2 ± 1.3 0.0002 Instrumental Activities of Daily Living 13.6 ± 0.8 12.1 ± 1.9 13.6 ± 1.2 12.4 ± 1.7 0.60 P-values computed using ANOVA models adjusted for stage and baseline scores. No significant financial relationships to disclose.
Commentary on "Nitric oxide synthase-derived plasma nitrite predicts exercise capacity"
Authors: Rainer Schulz
Journal: British Journal of Sports Medicine (2007)

<h3>Abstract</h3> Atypical processing of stimulus inputs across a range of sensory modalities in autism spectrum disorders (ASD) are widely reported. Sensory processing is known to be influenced by bodily internal states such as physiological arousal and anxiety. Since a sizeable proportion of ASD individuals reportedly have co-morbid anxiety disorders that are linked with dysregulated arousal, we investigated if face-emotion arousal cues, influenced visual sensory sensitivity (indexed by temporal resolution) in an ASD group (n=20) compared to a matched group of typically-developed individuals (TD, n=21). We asked further if emotion-cued changes in visual sensitivity associated with individual differences in state- and trait-anxiety. Participants reported the laterality of the second of two consecutive Gaussian-blob flashes in a visual temporal order judgment task (v-TOJ), demanding higher-level visual processing. The key manipulation was presenting a task-irrelevant face emotion cue briefly at unexpected time points preceding the task-relevant flashes. Disgust vs Neutral emotion signals enhanced the visual temporal resolution in ASD individuals. Furthermore, individual state-anxiety scores correlated with the emotion-cued change of temporal resolution (Disgust vs Neutral) in the ASD group. Both these effects were absent in the TD group. The results show that individual state-anxiety levels significantly modulate the effect of emotions on visual temporal sensitivity in ASD individuals, which was absent in our TD sample. The findings support a nuanced approach to understand the disparate sensory features in ASD individuals, by factoring in the interplay of the individual reactivity to environmental affective information and the severity of anxiety.
Endocrine outcome for children with embryonal brain tumors treated with craniospinal irradiation on the SJMB96 trial
Authors: A. Gajjar, T. Merchant, C. Sklar, D. Wallace, Z. Xiong, J. Shelso, A. Broniscer, M. Fouladi, L. Kun, S. Laughton
Journal: Journal of Clinical Oncology (2007)

9571 Background: To investigate the relationship between endocrine deficits with the radiation (RT) dose to the hypothalamic- pituitary axis (HPA) in medulloblastoma/PNET patients treated with risk-adapted craniospinal irradiation (CSI) followed by chemotherapy. Methods: 88 patients who survived at least 2 years from diagnosis were included in this analysis. CSI doses were 23.4 Gy or 36–39.6 Gy depending on clinical risk; the primary tumor site received 55.8 Gy. All pts had regular endocrine follow-up and screening to test for growth hormone (GH), thyroid hormone (TH) and adrenocorticotrophin hormone (ACTH) deficiency. Patients that had abnormal results on the screening tests underwent further evaluation by stimulation testing of the HPA. Only patients diagnosed with central hypothyroidism were included in the analysis for TH deficiency. Results: Of the 88 pts included in the study cohort, 77 pts had abnormal screening tests and underwent provocative testing. The median radiation dose to the hypothalamus was 42 Gy (26–57 Gy) and pituitary was 44 Gy (26–58 Gy). Patients receiving higher RT doses to the pituitary had a significantly higher incidence of growth hormone deficiency with 4-year estimates of 100 ±3% for those receiving = 44Gy and 82±7% for those receiving &lt; 44 Gy (p=0.024). Four-year estimates of thyroid hormone deficiency for patients receiving = 44 Gy to the pituitary were 67±21% and 18±14% for those receiving &lt; 44 Gy (p&lt;0.010). There was no correlation between the dose to the pituitary with the incidence of ACTH deficiency. The estimated change in height z-score for patients receiving &lt; 44 Gy to the pituitary was - 0.53 units per year (-0.44 to -0.63) compared with -0.70 units per year (-0.62 to -0.78) for those receiving = 44 Gy. Conclusions: Data from this prospective study demonstrate that RT to the HPA is the key determinant for developing endocrinopathies in patients with medulloblastoma/PNET. No significant financial relationships to disclose.
A survey of U.S. and Canadian oncologists’ attitudes toward the cost, cost-effectiveness (CE), and reimbursement of cancer drugs
Authors: P. Neumann, S. R. Berry, E. Nadler, W. C. Evans, J. Palmer, C. Bell, E. Strevel, H. Fang, P. A. Ubel
Journal: Journal of Clinical Oncology (2009)

9502 Background: Drug costs and reimbursement issues offer significant challenges to U.S. and Canadian oncologists even though they practice in substantially different health care systems. However, little is known about the attitudes of American and Canadian oncologists towards these issues. Methods: We surveyed 1,379 U.S. and 356 Cdn oncologists to assess their attitudes to cancer drug costs, CE and reimbursement policies. Results: Response rate was 57% in the U.S. and 48% in Canada. Oncologists in both countries stated that patients' “out-of-pocket” drug costs influenced their treatment recommendations (84% U.S., 80% Cdn respondents). Most respondents felt that every patient should have access to effective cancer treatments regardless of cost (66% US; 54% Cdn), while 59% of U.S. and 72% of Cdn and respondents believed that patients should only have access to effective cancer treatments that provided “good value for money.” 70% of U.S. and 64% Cdn respondents felt that &lt;$100,000 per life year gained was a reasonable definition of “good value for money” but less than half of respondents (42% US, 49% Cdn) felt well prepared to interpret and use CE information in their treatment decisions. A majority of respondents (57% US, 69% Cdn) felt government price controls for cancer drugs are needed while a minority felt that more cost-sharing by patients was needed (29% US, 37% Cdn). Most oncologists felt that evaluating whether a drug provides “good value” should be overseen by an independent non-profit agency (57% US, 71% Cdn) or physicians (61% US and Cdn); in contrast, few believed that government (21% US, 33% Cdn), patients (36% US, 37% Cdn) or insurance companies (6% US, 10% Cdn) should determine “good value”. 79% of U.S. and 69% of Cdn respondents felt more use of CE data in coverage and reimbursement decisions is needed. Conclusions: Oncologists in the U.S. and Canada share many similar attitudes to cancer drug costs, CE, and reimbursement policies despite differences in their health care systems. In both countries, oncologists favor more use of CE information. No significant financial relationships to disclose.