tbuckley/cabot-search huggingface dataset:
Adjuvant FOLFIRI with or without cetuximab in patients with resected stage III colon cancer: NCCTG Intergroup phase III trial N0147.
Authors: J. Huang, D. J. Sargent, M. R. Mahoney, S. N. Thibodeau, T. C. Smyrk, F. Sinicrope, G. D. Nelson, S. R. Alberts
Journal: Journal of Clinical Oncology (2011)

363 Background: Irinotecan (CPT-11) has demonstrated antitumor activity against metastatic colorectal cancer used alone or with 5-fluorouracil (5FU)/leucovorin (LV). Two arms with CPT-11, 5FU, and LV (FOLFIRI) +/- cetuximab (Cmab) were originally included in N0147. However, after CALGB 89803 (J Clin Oncol. 25:3456, 2007), PETACC-3 (J Clin Oncol. 27:3117, 2009), and Accord02 (Ann Oncol. 20:674, 2009) showed no benefit to the three-drug combination in adjuvant therapy, the CPT-11 arms of N0147 were discontinued. We report the outcomes for patients given FOLFIRI +/- Cmab. Methods: Following a signed informed consent patients with resected stage III colon cancer were randomized to one of 6 arms including 12 biweekly cycles of CPT-11 180 mg/m 2 d1 with LV 400 mg/m 2 , 5FU 400 mg/m 2 bolus IV, then 46-hr IV 5FU 2,400 mg/m 2 on d1-2 without (Arm B, FOLFIRI) or with Cmab (Arm E) 400 mg/m 2 d1 cycle 1 then Cmab at 250 mg/m 2 d1 and 8. Primary endpoint was 3-year disease-free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Results: 156 patients (Arm B-111, Arm E-45) were enrolled; median follow-up on 81 patients in Arm B was 60.3 months and 58.2 months in Arm E for 41 patients. wtKRAS (vs mt) status was associated with improved DFS (HR=0.6 [95% CI 0.4-1.1], p = 0.09) and OS (HR 0.7 [95% CI 0.4-1.5], p = 0.38). The addition of Cmab improved DFS and OS in the overall group and within wtKRAS pts. Grade greater than III non-hematologic adverse effects were significantly increased in the Cmab arm (46% vs. 64%, p = 0.05). Conclusions: In this randomized phase III trial adjuvant FOLFIRI resulted in a 3-year DFS lower than that expected for FOLFOX. Trends for improved DFS and OS with the addition of Cmab were observed in patients with resected stage III colon cancer patients, regardless of KRAS status. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. [Table: see text] [Table: see text]
Prevalence of HER2/neu overexpression/amplification in a Hispanic population with gastric adenocarcinoma.
Authors: M. Rodarte Shade, J. Flores Gutierrez, L. Garcia Labastida, L. Villela, A. Barbosa Quintana, A. Paredes Garcia, O. Gamboa, E. Guzman Huerta
Journal: Journal of Clinical Oncology (2011)

25 Background: In Europe, Asia, and North America, studies have identified that approximately 20% of patients with gastric adenocarcinoma exhibit overexpression of HER2/neu. This group of patients has been shown to benefit from combination therapy with the anti-HER2/neu monoclonal antibody trastuzumab. These findings have not been studied in Hispanics who may possess a distinct gastric cancer genotype. The aim of this study is to determine the rate of HER2/neu positivity in a completely Hispanic population with gastric adenocarcinoma and to analyze the clinical factors associated with HER2/neu. Methods: We conducted a retrospective study in three different hospitals in Monterrey, Mexico. The study population consisted of Hispanic patients with gastric adenocarcinoma who have had a gastric resection and for whom there were adequate amounts of tissue available in paraffin blocks. Tissue was tested for HER2/neu using both Immunohistochemistry (IHC) and the fluorescent in situ hybridization (FISH) techniques. Results: From 2000 to 2010, we initially evaluated 27 gastric cancer tumor samples. Sex distribution was 15 males and 12 females with a mean age of 57±15 (SD) years. Anatomic distribution of tumor was 4% in the cardias, 40% in the body and 56% in the antrum. Lauren's histological type distribution was 52% diffuse and 48% intestinal. Fifty-three percent of the tumors were high grade and nodal positivity was present in 69%. Overexpression of Her-2/neu (IHC ++ and +++) was found in five (17.4%) of the samples, being moderate (++) in two (7.4%) and strong (+++) in three (11%) tumor samples. FISH amplification for the HER2/neu gene was found in two (7.4%) tumors and was only seen in samples with a strong (+++) IHC result. There was no association identified between HER2/neu status with age, gender, degree of differentiation, T stage, or nodal status. Conclusions: In a homogeneous Hispanic population, 17.4% of gastric cancer patients were found to overexpress HER2/neu by IHC. FISH did not identify any additional HER2/neu positive tumors. It is important to consider IHC testing for HER2/neu in Hispanic gastric cancer patients as they could benefit from a chemotherapy regimen containing trastuzumab. No significant financial relationships to disclose.
High-dose remote afterloading intraluminal brachytherapy in the treatment of unresectable hilar or upper bile duct carcinoma.
Authors: H. Andoh, Y. Shindo
Journal: Journal of Clinical Oncology (2011)

273 Background: To evaluate intraluminal brachytherapy (ILBT) for the treatment of unresectable hilar or upper bile duct carcinoma. Methods: Between 1992 and 2005, 48 patients were identified who were not indicated for surgical resections. Among them, 22 patients received only biliary drainage (group I) and 26 patients received ILBT (group II). Expandable metallic stents (EMSs) were used in 17 patients and ILBT was delivered using the Varisource 200 remote afterloading unit with a 10 Ci 192 Ir or 60 Co. Each treatment of ILBT delivered 6 Gy at a 1-cm depth, and was repeated weekly for 5 weeks. A total of 30 Gy was administered to each patient. Survival rates between the groups were compared using Kaplan-Meier survival curves. Results: In group I, survival rates at 6 and 12 months were 9% and 0%, respectively. Median survival was only 2 months. In contrast, group II survival rates at 6, 12, and 24 months were 77%, 54%, and 9%, respectively, and the median survival of this group was 13 months. Improved survival with the use of ILBT was significant, particularly in clinical stages III, IVa (p&lt;0.01), and IVb (p&lt;0.05). ILBT helped keep the bile duct lumen patent for a long period, but was not effective for the treatment of patients with positive lymph node metastasis. Conclusions: Although randomized controlled studies will be necessary, the results of the present study are encouraging for using high-dose ILBT in the treatment of unresectable hilar or upper bile duct carcinoma without lymph node metastasis. No significant financial relationships to disclose.
Association between daytime activity, sleep, and symptom burden in patients with advanced cancer: A preliminary report.
Authors: Sriram Yennu, Supakarn Tayjasanant, Dave Balachandran, Nikhil S Padhye, Janet L. Williams, Diane D Liu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

101 Background: There is limited research in advanced cancer patients (ACP) regarding association between objective daytime activity, sleep variables and symptom burden. Our primary aim was to determine the association between mean daytime activity (MDTA) and objective sleep variables, cancer related fatigue (FACIT-F), symptom burden (ESAS), Anxiety and Depression (HADS), Sleep Quality (PSQI) and overall survival (OS). Methods: Secondary analysis of a recent clinical trial of cancer related fatigue in advanced cancer (NCT00424099). Association between MDTA and sleep variables (measured by actigraphy) during the first week of the study and patient characteristics, symptoms (FACIT-F, ESAS, HADS, and PSQI) and OS were analyzed using Spearman correlation, multivariate analysis and survival analysis. Results: 79 eligible patients were evaluable. The median age was 57 years. Median MDTA was 248.43 counts/min. MDTA was significantly associated with (r, p-value) age (-.379, ≤ .001), serum albumin (.328, .006), FACT-Functional well-being (FWB) (.248, .028), ESAS dyspnea (-.300, .008), HADS-Anxiety (.262, P = .019) and total sleep time (-.323, .004). MDTA was not associated with FACIT-F subscale (p = .997) and OS (p = .18). PSQI was significantly associated with FACIT-F, HADS, ESAS anxiety and depression, but none of these variables were associated with sleep measured by actigraphy. Conclusions: In ACP, lower MDTA was not correlated with patient reported fatigue, and sleep measured by actigraphy was not associated with patient reported sleep disturbance. Both fatigue and sleep disturbance were strongly associated with depression and anxiety. More research is needed to characterize the association between objective and patient reported daytime activity, fatigue and sleep. Clinical trial information: NCT00424099.
Relationship of oral acetaldehyde concentration and oral microflora with the development of superficial pharyngeal or esophageal squamous cell carcinoma.
Authors: Toshiro Iizuka, Daisuke Kikuchi, Shu Hoteya, Mamoru Tanaka, Mitsuru Kaise
Journal: Journal of Clinical Oncology (2013)

57 Background: Acetaldehyde in alcoholic beverages is evidently carcinogenic to the pharynx and esophagus. The relationship between microflora in the gastrointestinal tract and carcinogenesis, such as that between Helicobacter pyloriand gastric cancer, has attracted attention; however, there are few reports of oral microflora influencing the developing the squamous cell carcinoma of the pharynx or esophagus. Therefore, we investigated factors that might influence the development of cancer in the pharynx and esophagus. Methods: A total of 82 patients participated in this study and consisted of 50 with pharyngeal or esophageal cancer treated by endoscopic submucosal dissection and 32 with no cancer. Chromosomal DNA was extracted from bacteria in the oral mucosa, and terminal restriction fragment length polymorphism analysis was carried out. The concentration of acetaldehyde in saliva was measured, and clinical factors were assessed by multivariable analysis. Results: The average values of clinical parameters in patients with pharyngeal or esophageal cancer were as follows: age, 68 years; acetaldehyde, 2.5 μmol/l; GOT, 30.5 IU/l; GPT, 23.5 IU/l; γGTP, 79.4 IU/l; Hb, 14.1 g/dl; MCV, 97.6 fl; alcohol consumption, 6.1 g/day; and Brinkman index, 764. In patients with no cancer, the same parameters were as follows: age, 69 years; acetaldehyde, 4.8 μmol/l; GOT, 23 IU/l; GPT, 21.9 IU/l; γGTP, 36.9 IU/l; Hb, 14.2 g/dl; MCV, 93.7 fl; alcohol consumption, 1.9 g/day, and Brinkman index, 350. Multivariable analysis showed that acetaldehyde concentration (odds ratio: 0.63; 95% CI: 0.47–0.85) and alcohol consumption (odds ratio: 1.64; 95% CI: 1.19–2.25) were significantly different between the two groups. Cluster analysis extracted 16 small clusters from the dendrogram. In 3 clusters among them, the percentage of patients with cancer was more than 80%. Conclusions: Cluster analysis revealed three clusters with a high incidence of cancer patients. Therefore, acetaldehyde concentration and alcohol consumption may be related with carcinogenesis of the pharynx and esophagus. We intend to identify the microbial flora of each cluster in a future study.
A phase II study of gemcitabine (G), bevacizumab (B), and erlotinib (E) in locally advanced (LAPC) and metastatic adenocarcinoma (MPC) of the pancreas
Authors: L. S. Blaszkowsky, A. X. Zhu, T. A. Abrams, C. C. Earle, E. Kwak, A. F. Hezel, J. A. Meyerhardt, K. Horgan, H. Zheng, D. P. Ryan
Journal: Journal of Clinical Oncology (2008)

15515 Background: Clinical trials evaluating combination therapy for pancreatic cancer have been disappointing. The addition of E to G has resulted in a modest, yet statistically significant improvement in progression-free, overall, and 1-year survival, without an improvement in response rate, while the addition of B to G, has failed to prove beneficial. In an attempt to capitalize on the lack of overlapping toxicities and potential enhancement of activity of epidermal growth factor receptor inhibitors as demonstrated in colorectal cancer, we initiated this study to determine the safety and efficacy of adding B to G and E. Methods: Thirty patients (pts) with LAPC or MPC who had adequate hepatic, renal and hematopoietic function, and ECOG performance status of 0–1, were registered. Treatment consisted of G 1,000 mg/m2 intravenously (IV) on days 1, 8, and 15, E 100 mg orally days 1–28, and B 10 mg/kg IV days 1 and 15, every 28 days. Tumor measurements were performed every 8 weeks. Pts were assessed for radiologic response (RECIST), time to tumor progression (TTP), median overall survival (MS), 1-year survival, and toxicity (TOX). Results: Twenty-eight pts began study therapy. Two pts never began study therapy: 1 pt withdrew consent and another experienced a massive pulmonary embolus (PE) prior to treatment. In addition, 1 pt experienced an upper GI bleed and did not complete 1 cycle and 1 pt did not have restaging scans. Of the 28 treated pts, 3 had LAPC and 25 had MPC. Response data is available on 23 pts. There were 5 (22%) partial responses, 4 (17%) confirmed partial responses, 13 (57%) with stable disease, and 6 (26%) with progressive disease. The median TTP was 3.5 (95%CI 2.6–5.2) months. The MS was 6.8 (95%CI 5.3-not estimatable) months. Grade 3–4 treatment-related TOX included: 6 (27%) neutropenia, 2 (7.7%) SGOT, 2 (7.7%) SGPT, 3 (11.5%) fatigue, 2 (7.7%) acneform rash, 1 (3.8%) duodenal hemorrhage, 1 (3.8%) PE and 1 (3.8%) arterial event. Conclusions: The combination of G, E and B was well tolerated, and shows modest activity in pts with locally advanced and metastatic pancreatic cancer. Supported by Genentech. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology
Effect of increased MET gene copy number on survival of surgically resected non-small cell lung cancer (NSCLC) patients
Authors: F. Cappuzzo, M. Skokan, S. Gajapathy, L. Giordano, M. Incarbone, M. Roncalli, L. Terracciano, M. Alloisio, A. Santoro, M. Varella-Garcia
Journal: Journal of Clinical Oncology (2008)

11047 Background: MET, the gene codifying for hepatocyte growth factor receptor, is a novel molecular target in NSCLC. MET is amplified in 20% of NSCLC patients with Epidermal Growth Factor Receptor (EGFR) mutations progressing after initial response to EGFR-Tyrosine Kinase Inhibitor (TKI) therapy. Nevertheless, the incidence of MET gene gain in EGFR-TKI naïve NSCLC and its impact on prognosis remain unreported. The present study evaluated the association between MET gene copy number, clinical characteristics and survival in surgically resected NSCLC. Methods: The study cohort included 447 patients mainly in pathological stage I-II (265/59.2%), male (373, 77.6%), former/current smokers (389, 87.1%), with adenocarcinoma histology (241, 53.9%). MET was evaluated by fluorescence in situ hybridization (FISH) in tissue microarray sections from primary lung tumors. Results: MET FISH analysis was successfully performed in 410 cases, and high MET gene copy number (mean ≥ 5 copies/cell) was observed in 43 cases (MET+, 10.4%), including 18 cases with gene amplification (4.3%) and 25 cases with high polysomy (6.1%). MET+ status was significantly associated with advanced stage (p%0.03), with no significant association with gender, smoking history, histology or grading. In the whole population, MET+ patients had a significantly shorter survival than MET- (3-year survival 35.7% versus 58.3%, median survival 25 versus 47 months, HR:1.61, p%0.007). In pathologically stage I-II disease, 3-year survival (50.0% versus 72.5%) and median survival (33 months versus not reached) were significantly shorter in MET+ individuals (HR:1.89, p%0.03). In adenocarcinoma with or without BAC features, MET+ had a significantly shorter 3- year survival (28.6% versus 56.4%) and median survival (24 versus 44 months) than MET- (HR:2.08, p%0.003). Multivariable model confirmed that in stage I-II disease MET was an independent prognostic factor (HR:1.90, p%0.05). Conclusions: MET increased gene copy number is associated with poor prognosis in surgically treated patients. True gene amplification is a rare event, which suggests a marginal role of MET in intrinsic resistance to EGFR-TKI therapy. High copy numbers by polysomy is more frequent and its impact must be investigated. No significant financial relationships to disclose.
Response of blood flow to hyperthermia in human prostate tumors: Opportunities for enhanced radiation effect and drug delivery.
Authors: Mark Hurwitz, Gregory T Martin, Daniel A Sidney, Charles J Welch, Jorgen L Hansen, Bruce A Bornstein, Irving D. Kaplan, H F Bowman
Journal: Journal of Clinical Oncology (2014)

189 Background: Tissue perfusion may be a significant factor affecting outcome of prostate cancer treatment. Hyperthermia has been shown to have beneficial anti-cancer effects when combined with other anti-neoplastic modalities including radiation, chemotherapy, and immunotherapy. For instance, hyperthermia may increase prostate perfusion resulting in radiosensitization through increased oxygenation and chemotherapy through enhanced drug delivery. We previously reported significant benefit to the addition of hyperthermia to radiation on a phase II trial for men with locally advanced prostate cancer. To better understand tissue perfusion in patients with prostate cancer and response to hyperthermia, we measured perfusion levels in patients on this trial before and after hyperthermia. Methods: Prostate perfusion was measured before and immediately after heating in a total of 21 hyperthermia treatments in 14 patients with prostate cancer. A trans-rectal ultrasound device with a water cooled jacket was used to heat the prostate. Prostate tissue temperatures were measured using three multisensory thermocouple probes. Perfusion was measured with the TDP-200 Thermal Diffusion Probe, a thermistor-based device which quantifies perfusion with a modified wash-out technique. Results: In 19 treatments in which perfusion was measured before heating, average and standard deviation was 18.3 ± 10.6 ml/100g-min and in 17 treatments in which perfusion was measured after heating, it was 30.7 ± 20.8 ml/100g-min. This represents a statistically significant increase of 68% (p = 0.018). Perfusion increased 12 of 15 treatments in which measurements were obtained before and after hyperthermia. Notably, prostate tissue that was most ischemic prior to heating experienced the largest heat-induced perfusion increase. Conclusions: Prostate perfusion increased significantly with a majority of hyperthermia treatments. Enhanced prostate oxygenation may have been a contributing factor to the benefit noted with hyperthermia in this phase II trial. The use of hyperthermia to augment prostate perfusion to enhance radiation, chemotherapy, and immunotherapy warrants further investigation.
The impact of initial surgery at a cancer hospital on the outcome of retroperitoneal sarcomas
Authors: R. L. Neff, S. Sharif, O. Al Saif, S. Nag, J. Grecula, M. Walker
Journal: Journal of Clinical Oncology (2008)

10597 Background: The considerable morbidity, mortality and relative rarity of retroperitoneal sarcoma demands an experienced institution to achieve better clinical outcomes. Methods: From the surgical oncology sarcoma database, the charts of 44 patients (pts) with primary retroperitoneal sarcoma from 1989 to 2005 were retrospectively reviewed. Those pts with primary surgery performed at The James Cancer Hospital of The Ohio State University (CHRI) were compared to those who underwent initial surgery at a non-tertiary care center and subsequently were referred for intra-abdominal recurrences. Data were compared with Fisher’s exact test and Student’s t-test where appropriate. Results: Thirty-three pts underwent initial resection of a retroperitoneal sarcoma at CHRI whereas 11 pts underwent initial surgery elsewhere. On univariate analysis, there were no significant differences between the two groups with regard to age, gender, histologic type, grade or disease free interval. Initial surgery at CHRI was more likely to produce an R0 resection (79% vs. 36%, p<0.05) with subsequent negative margins. Preoperative chemoradiation and postoperative chemotherapy were more prevalent for pts treated initially at CHRI than at the outside (36% vs.18%, p>0.05). There was no significant difference in disease-free interval between the two groups from initial surgery to first recurrence (14 mo.s vs. 18 mo.s, p>0.05). Intra-operative radiation (IORT) was utilized in 21 of the 44 pts and had a significant impact on decreasing intra-abdominal recurrence (28% vs. 74% p<0.05). Seven of the 11 pts reoperated on at CHRI underwent IORT with a median follow-up of 30 months. On subgroup analysis, the survival of Grade 1 retroperitoneal sarcomas was significantly better for patients initially operated at CHRI, 61 mo.s vs. 43 mo.s, p<0.05. Hovever, there was no difference in cancer mortality between the two groups (39% vs. 45%, p>0.05). Conclusions: The utilization of multimodality therapy in the initial treatment of retroperitoneal sarcoma was significantly greater in pts treated at CHRI. The surgical therapy resulted in increased R0 resection and decreased intra-abdominal recurrence which led to a greater survival in the subgroup of grade 1 patients. No significant financial relationships to disclose.
Associations between health-related quality of life and physical activity in bladder cancer survivors: A cross-sectional study.
Authors: Ajay Gopalakrishna, Joseph J Fantony, Thomas Andrew Longo, Brant Allen Inman
Journal: Journal of Clinical Oncology (2016)

432 Background: Physical activity has been shown to significantly improve health-related quality of life (HRQOL) and survivorship in a variety of cancer patients. However, little is known about the physical activity patterns of bladder cancer survivors and how these are related to HRQOL in the United States. Our objective was to describe HRQOL and self-reported physical activity patterns and examine the association between these measures in a large cohort of bladder cancer survivors. Methods: Bladder cancer survivors identified through an institutional database were mailed a survey that included the Functional Assessment of Cancer Therapy Bladder Cancer (FACT-Bl) and the International Physical Activity Questionnaire (IPAQ-L). Results: A total of 466 subjects (49% response rate) completed the survey. The mean age was 73 years, 80% were male, and 88% were White. Linear regression indicated a positive correlation between physical activity and physical well being (PWB, P &lt; 0.001), emotional well being (EWB, P &lt; 0.001), and functional well being (FWB, P &lt; 0.001) subscales, as well as the FACT-Bl (P &lt; 0.001), FACT general (P &lt; 0.001), and trial outcome index (TOI, P &lt; 0.001) composite scores. Conversely, total daily sitting time was negatively correlated with all of the aforementioned indices. Adjusting for demographic factors did not alter the findings. Conclusions: Physical activity is positively associated with HRQOL in bladder cancer survivors. Further studies investigating the causal relationship between physical activity and HRQOL in the post-treatment setting in bladder cancer survivors are warranted.