tbuckley/cabot-search huggingface dataset:
The role of metformin for primary prevention in non-elderly diabetic colorectal cancer patients.
Authors: Amikar Sehdev, Ya-Chen T. Shih, Benjamin Vekhter, Christopher Lyttle, Blase N. Polite
Journal: Journal of Clinical Oncology (2014)

406 Background: There is growing evidence for the beneficial effect of metformin in reducing the incidence of colorectal cancer (CRC) in diabetic patients. However, no such studies are done in the US population. We conducted a case control study (N=8,046) in non-elderly diabetic adult US population (age 18-64 years) to investigate the role of metformin for the primary prevention of CRC. Methods: MarketScan claims database was used to identify diabetic patients with CRC using ICD-9 codes. Only incident cases of CRC in diabetic patients were included in the study. Two matched controls (matched for age, sex, and geographical region) were selected per case. The exposure to metformin was assessed from prescriptions in the 12 months prior to the earliest date of CRC diagnosis. The primary objective was to assess the odds of having CRC in metformin users as compared nonusers. Adjusted odds ratios (AOR) were calculated by adjusting for multiple potential confounders using conditional logistic regression. Results: The mean age of CRC patients was 56 years, 60% were males. Metformin was prescribed to 38.13% patients. A total of 37% (995/2,682) patients developed CRC in metformin exposed group compared to 62.9% (1,687/2,682) patients in non-metformin exposed group. In a multivariate model, any metformin use was associated with a statistically significant 12% reduced risk of developing CRC (AOR 0.88, 95% CI, 0.79-0.98, p&lt;0.026). Prescribed NSAIDs were also associated with decreased incidence of CRC (AOR 0.84, 95% CI, 0.73-0.97, p=0.019). Variables associated with increased incidence of CRC in the multivariate model were IBD (AOR 1.94, 95% CI, 1.13-3.33, p&lt;0.015); use of insulin (AOR 1.45, 95% CI, 1.27-1.65, p&lt;0.001); coronary artery disease (AOR 1.66, 95% CI, 1.43-1.93, p&lt;0.001). There was no significant relationship between CRC incidence and obesity (AOR 1.19, 95% CI, 0.93-1.53, p=0.158); polycystic ovary disease (AOR 0.32, 95% CI, 0.03-2.76, p=0.3); sulfonylureas (AOR 1.09, 95% CI, 0.96-1.24, p=0.15); thiazolidinediones (AOR 0.94, 95% CI, 0.82-1.08, p=0.41); statins (AOR 0.914, 95% CI, 0.82-1.01, p=0.108). Conclusions: The use of metformin appears to reduce the incidence of CRC in non-elderly diabetic adult US population.
Combination of docetaxel and cisplatin for recurrent nasopharyngeal carcinoma: Preliminary results
Authors: K. A. Benhadji, M. Yamouni, Y. Beldjilali, D. Yekrou, M. Brahimi, W. Chabou, L. Djellali
Journal: Journal of Clinical Oncology (2005)

5602 Background: Recurrent nasopharyngeal carcinoma (NPC) after primary treatment with chemotherapy and radiation therapy has not a standard therapy. The purpose of this study is to assess the antitumor activity and toxicity of docetaxel (D) plus cisplatin (C) in this situation. Methods: Patients (pts) with recurrent undifferentiated NPC were enrolled in this study. Pts received D 35 mg/m2 and C 35 mg/m2 both on days 1.8 and 15. Cycles were repeated every 28 days. Primary end point was tumor response. Results: A total of 17 pts were enrolled. There are 13 male and 4 female with a median age of 38 years (range 23 - 62) and a performance status (WHO) of 1 in 5 pts and 2 in 12 pts. All patients were pretreated with a cisplatin based chemotherapy in combination with sequential or concomitant radiation therapy. Sites of recurrences are detailed in the table below. After 108 cycles, grade 3 & 4 toxicity (WHO) were: neutropenia (3%), nausea and vomiting (3%), reversible alopecia (8%). Response rates for the 17 pts were: partial response 29.5% (5 pts), stable disease 41% (7 pts) and progression 29.5% (5 pts). The median survival was 8.5 months; time to progression was 5.6 months. Conclusions: DC combination has shown a modest activity further investigation is needed to evaluate disease free survival and survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
A prospective randomized phase III trial comparing consolidation therapy with or without strontium-89 following induction chemotherapy in androgen-independent prostate cancer.
Authors: Jennifer Wang, Shi-Ming Tu, Lance C. Pagliaro, Matthias Weiss, Julio Hajdenberg, Jennifer Tseng, James Lloyd Wade, Robert J. Belt, Michael W. Cannon, Michael Fisch
Journal: Journal of Clinical Oncology (2014)

90 Background: New therapies have shown benefit for advanced prostate cancer, but are not curative. Bone metastases cause significant prostate cancer morbidity. Preliminary studies showed that bone-targeted therapy with strontium-89 (Sr-89) with doxorubicin was feasible in patients with stable or responding metastatic castration-resistant prostate cancer (mCRPC) after KAVE (ketoconazole and doxorubicin alternating with estramustine and vinblastine) induction with promising time to progression (13.9 vs. 7.0 months) and overall survival (27.7 vs. 16.8 months). We conducted this phase III, randomized, double-blind, multicenter study to determine the effectiveness of consolidation therapy with or without Sr-89. Methods: Patients with progressive mCRPC with bone disease received induction with KAVE or docetaxel/prednisone (D) chosen by the treating physician. Patients with stable or responding disease were randomized at week 16 to receive doxorubicin with either one dose (4 mCi) or no Sr-89. Primary endpoint was overall survival (OS). Results: This study was activated in April 2002 with planned randomization of 480 patients (240 patients per study arm). The trial closed early with a total of 265 patients: median age 67; median prostate-specific antigen (PSA) 71.2; 109 received KAVE; 155 received D, 127 (47.9%) patients went on to randomization, 43 (39.4%) from the KAVE arm, and 84 (54.2%) from the D arm. Multivariate Cox proportional hazards regression was used to control for induction regimen, Eastern Cooperative Oncology Group (ECOG) status, and number of bone metastases. Median survival from times of registration and randomization in the no-Sr-89 arm were 26.5 months (95% CI: 21.1, 29.9) and 22.8 months (95% CI: 17.7, 26.1), respectively, compared to 27.9 months (95% CI: 23.6, 34.2) and 24.3 (95% CI:19.8, 29.9) months in the Sr-89 arm. OS from registration (p=0.61) and randomization (p=0.62) were not statistically significant on univariate or multivariate analyses. Conclusions: The addition of Sr-89 to consolidation chemo did not improve OS in this study. This community-based, multicenter study closed prematurely due to slow accrual, demonstrating challenges in conducting trials in the US that combine radionuclide therapy with chemotherapy. Clinical trial information: MDA 3410.
Using anastrozole as initial adjuvant treatment prevents early recurrences and reduces adverse events: Updated data from the ATAC (‘Arimidex’, Tamoxifen, Alone or in Combination) trial
Authors: J. Houghton
Journal: Journal of Clinical Oncology (2005)

582 Background: Recent interest in the delayed introduction of aromatase inhibitors (AIs) as adjuvant therapy after tamoxifen has highlighted the need to evaluate the relative effectiveness of AIs and tamoxifen over the standard 5-year adjuvant period. Methods: The ATAC trial is a double-blind, randomized trial designed to compare anastrozole (n=3125) with tamoxifen alone (n=3116) or in combination with anastrozole (n=3125), as adjuvant therapy in 9366 postmenopausal women with early breast cancer. The ATAC trial is currently the only trial to have reported long-term direct comparisons of the efficacy and tolerability of an AI with tamoxifen. Results: A total of 1226 first events in the two monotherapy arms were included in the recent ATAC completed treatment analysis (median follow-up 68 months). Anastrozole continued to demonstrate a significantly lower number of first events compared with tamoxifen (575 vs 651, respectively; HR 0.87; 95% CI: 0.78, 0.97; p=0.013), and was associated with a beneficial additional event profile (Table). Conclusions: Initiating tamoxifen treatment with the intention of switching to an AI after 2.5 or 5 years would lose these early benefits of anastrozole over tamoxifen. The higher rates of recurrence, AEs and withdrawals associated with adjuvant tamoxifen at 2.5 and 5 years justify offering adjuvant therapy with anastrozole at the earliest opportunity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Prognostic significance of indeterminate lung nodules in renal cell carcinoma.
Authors: Rena Xu, Nora Horick, Francis J. McGovern, Douglas M. Dahl, Adam S. Feldman, Michael L. Blute, Aria F. Olumi, M. Dror Michaelson
Journal: Journal of Clinical Oncology (2013)

377 Background: Many patients with newly diagnosed renal cell carcinoma (RCC) are found to have indeterminate lung nodules at the time of diagnosis. Current guidelines are vague about the necessity and frequency of additional chest imaging. We sought to determine whether the presence of indeterminate lung nodules at the time of diagnosis affects long-term survival for patients with early stage RCC. Methods: A retrospective review was performed of all patients at our institution who underwent nephrectomy for stage I-III RCC between 2001 and 2006 and had baseline chest imaging available for review. Presence of indeterminate lung nodule(s) on preoperative chest imaging was determined, along with tumor stage, grade, and histology; patient age, gender, body mass index, and smoking status; and Charlson comorbidity score. The time from diagnosis to last documented follow-up, and to first detected metastasis and/or death if applicable, was determined. Univariate and multivariate analyses were performed. The primary outcome of interest was disease-free survival; the secondary outcome was overall survival. The study follow-up period extended to July 2012. Results: In a multivariate analysis of 240 patients, disease-free survival was significantly associated with the presence of indeterminate lung nodules (HR 1.900, 95% CI: [1.042, 3.463]; p = 0.036). The number and size of the nodules did not add statistical significance. Disease-free survival was also associated with tumor stage (stage II: HR 5.611, p &lt; 0.001; stage III: HR 2.488, p = 0.0129) and grade (HR 2.433 for grade 3 or 4, p = 0.005). Overall survival was only associated with Charlson comorbidity score (HR 1.294, p &lt; 0.0001) and primary tumor size (HR 1.287, p &lt; 0.0001). Conclusions: The presence of indeterminate lung nodules at the time of diagnosis of RCC had a negative impact on disease-specific survival. Tumor stage and grade were also significant prognostic factors. These findings underscore the importance of baseline chest imaging as well as vigilant surveillance of patients in whom lung nodules are identified.
Circulating biomarkers exploratory study in loco-regional gastroesophageal adenocarcinoma patients.
Authors: Federico Longo, Julie Earl, Jose Carlos Martinez-Avila, Carme Guerrero, Vanesa Pachon, Mercedes Rodríguez Garrote, REYES Ferreiro, Ana Gómez Rueda, Javier Molina, Maria Villamayor Delgado, Olga Martinez Saez, Alfonso Cortes Salgado, Jacobo Muñoz del Toro, Silvia Patricia Cortez Castedo, Maria Eugenia Olmedo Garcia, Pedro Lopez Hervas, Pablo Priego, Julio Galindo, Carmen Guillén Ponce, Alfredo Carrato
Journal: Journal of Clinical Oncology (2016)

17 Background: Patients diagnosed with gastroesophageal adenocarcinoma (GEA) have a poor prognosis despite curative attempts with multimodal treatment including surgery, chemotherapy (CT) and radiotherapy (RT). VEGF, EpCAM, MUC1, CK19 and CK20 and CD133 have shown to provide additional prognostic information in advanced GEA patients. Methods: Circulating mRNA of total VEGF (and 2 VEGF isoforms 121 and 165), EpCAM, MUC1 and CD133 were determined in 36 loco-regional GEA patients (pts). Blood samples were collected before surgery or, when indicated, before the preoperative chemotherapy treatment, within a 7 days window. Additionally, 14 healthy volunteers and 7 advanced GEA pts were included to comparative analyses. The Wilcoxon test was used to assess differences in expression among the groups. Results: Pre-surgery CT was administered in 30 pts (79%). ECF or its modifications were administered in 22 pts, and FOLFOX in 7 pts. Type of resection achieved was R0 (19 pts, 59%), R1(7 pts, 22%) and R2 (6 pts, 10%). Post-surgery CT was administered in 22 pts (73%) including ECF or its modifications (10 pts), FOLFOX (7 pts) and CT-RT (4 pts). PFS occurred in 19 pts (61%) and 34 patients remained alive at the time of this analysis. Patients diagnosed with loco-regional GEA exhibited over expression as compared to healthy volunteers of VEGFi121 in 17 pts (47%) by 33-fold median change (IQR 5-43, %, p = 0.0008); VEGFi165 in 17 pts (47%) by 15-fold (IQR 5-36, p = 0.002); total VEGF in 19 pts (53%) by 15 fold (IQR 8-59, p = 0.01); EpCAM in 8 pts (22%) by 3-fold (IQR 0.5-3, NS); MUC1 in 19 pts (53%) by 23-fold (IQR7-59, p = 0.0008); and CD133 in 2 pts (6%) by 55-fold (IQR 28-83, NS). CK20 expression was not detected in healthy controls but was detected in 3 patients. Conclusions: VEGF and its isoforms VEGF121 and VEGF165 and MUC1 are potential diagnostic biomarkers in GEA. Due to the short follow-up of patients we cannot yet evaluate their role as prognostic biomarkers.
Activation of p53 Signaling Is Synergistically Enhanced by Bcl-2 Inhibition through Induction of Noxa and Bak/Bax Heterodimers Resulting in Apoptosis of AML Stem Cells
Authors: Marina Konopleva, Twee Tsao, Xiaoyang Ling, Kensuke Kojima, Julie Watt, Duncan H. Mak, Monique Verhaegen, William Bornmann, Maria Soengas, Michael Andreeff
Journal: Blood (2008)
Positron emission tomography-computed tomography (PET-CT) for the assessment of pathologic response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma.
Authors: Noman Ashraf, Saqib Razzaque, Ben C. Creelan, Julio C. Chavez, David Shibata, Sarah Hoffe, Ravi Shridhar, Richard D. Kim
Journal: Journal of Clinical Oncology (2013)

537 Background: Preoperative 5-fluorouracil and radiation (FU-XRT) has been demonstrated to improve recurrence-free survival in locally advanced rectal adenocarcinoma, however the role of interval PET-CT remains unclear. We performed a retrospective study with the primary objective of examining the association of change in standardized uptake value (SUV) by PET-CT after neoadjuvant chemoradiation and pathologic complete response (path CR) to survival. Methods: Data was extracted for cases at our institution between August 2006–August 2009, with last follow-up performed July 2012. Patients were included if (i) they had completed a full course of preoperative FU-XRT, followed by surgery with intent for R0 resection, and (ii) pre- and post- therapy PET-CT as well as pathologic reports were available for review. Data was compared by Fischer's exact and Wilcoxon rank-sum, and survival was analyzed using Kaplan-Meier method. Clinicopathologic data was compared by log-rank test and univariate Cox proportional hazards for relationship to overall survival (OS). Results: Of 128 total rectal cancer cases reviewed, 25 (19%) met inclusion criteria. Characteristics of 25 patients included: 13 female, age 57± 14 years (median ± SD). After 116 patient-years of follow-up, median OS was not reached; mean OS was 4.6 ± 0.9 years. Mean baseline pre-treatment PET SUV (18.5 ± 9.1) decreased after neoadjuvant FU-XRT (5.0 ± 4.3, p &lt; 0.0001). Five achieved path CR. Presence of earlier stage was associated with non-significant trend towards improved chance of pathologic CR (RR 3.1, p = 0.07). A decrease in PET SUV by 80% or more was associated with improved odds of path CR (OR 25, 95% CI 1.2 - 513, p = 0.009), and was also associated with a non-significant trend towards improved OS (HR 0.19, 95% CI 0.01 - 2.7). Path CR was associated with a non-statistically significant trend to improved overall survival (HR 0.28, 95% CI 0.01 - 8.4). Conclusions: Reduction in PET-CT SUV after neoadjuvant chemoradiation may be a useful predictor of pathologic CR in rectal adenocarcinoma. These exploratory findings need to be validated in larger prospective studies.
The therapeutic effect of irreversible electroporation ablation in mouse model of gastrointestinal cancer.
Authors: Hyuk Soon Choi, Hoon Jai Chun, In Kyung Yoo, Jae Min Lee, Seung Han Kim, Eun Sun Kim, Bora Keum, Yoon Tae Jeen, Hong Sik Lee, Chang Duck Kim
Journal: Journal of Clinical Oncology (2016)

62 Background: Irreversible electroporation (IRE) is a promising novel technique for the ablation of tumors. IRE has an advantage over other ablation technique in its mechanism to remove undesired cells by affecting the cell membrane without thermally destructing blood vessels, nerves and the surrounding tissues. Studies regarding the clinical application of IRE have been performed in humans, as well as in animals, for organs such as the liver, kidney, prostate, etc. and IRE is now accepted as a novel anti-cancer ablation modality. The aim of this study was to evaluate the therapeutic effect of IRE in mouse model of gastrointestinal cancer for the first time. Methods: The Caco2 cells (ATCC) were cultured in petri-dishes. Male nude mice (Immunodeficient (CAnN.Cg-Foxn1 nu/CrljBgi) 6 weeks old, Orient Inc., Korea) were introduced. Caco2 cells were each visually injected at 1.0 x 10 7 cells/ml into both flakes (one for control, the other for IRE). We performed in vivo IRE procedures in the tumors of nude mouse model. Electrical pulses were applied to the tumor of nude mouse using a DC generator at 1~2kV/cm amplitude, 20~50 pulses, 100 µA length, with 1mm separation between two needle type electrodes. We analyzed the tissues with H&amp;E staining and TUNEL assay immediately afterwards, and then 10 hours, 24 hours. Results: All mice were preserved during the experiment without significant complications. There was complete cell death within the IRE lesions without intervening live cells in 2KV after 24 hours. H&amp; E statin and Tunnel stain at 10hr after 2KV IRE ablation revealed more severe apoptotic cell death comparing with control group. Apoptotic index peaks at 10 hours after IRE ablation, and decreases in 24hours. The framework of extracellular matrix and blood vessels were not affected by IRE. Conclusions: The present study demonstrated that IRE ablated colon cancer tissue very effectively through the induction of cellular apoptosis. This study suggests that IRE has the potentiality in treatment of gastrointestinal cancer patients.
Randomized Comparison of Standard Induction with Daunorubicin (DNR) for 3 Days vs Idarubicin (IDA) for 3 or 4 Days in AML pts Aged 50 to 70 and of Maintenance with Interleukin 2. Final Analysis of the ALFA 9801 Study.
Authors: Cecile Pautas, Xavier Thomas, Fatiha Merabet, Emmanuel Raffoux, Jean Henri Bourhis, Stephane de Botton, Oumedaly Reman, Pascal Turlure, Claude Gardin, Nathalie Contentin, Thierry de Revel, Isabelle Plantier, Philippe Rousselot, Claude Preudhomme, Pierre Fenaux, Maud Janvier, Christine Terre, Herve Dombret, Mauricette Michallet, Sylvie Chevret, Sylvie Castaigne
Journal: Blood (2007)
Intersalt: An international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion
Authors: G. Rose, J. Stamler, R. Stamler, P. Elliott, M. Marmot, K. Pyorala, H. Kesteloot, J. Joossens, L. Hansson, G. Mancia, A. Dyer, D. Kromhout, U. Laaser, S. Sans
Journal: BMJ (1988)
A novel method for decreasing rectal toxicity during prostate radiotherapy by prostate-rectum separation: An evaluation of irradiation dose parameters and acute side effects.
Authors: Michael J. Mathers, Theodor Klotz, Yvonne Lazar, Thomas Eckl, Horst Hermani, Bernd Gagel
Journal: Journal of Clinical Oncology (2013)

227 Background: Prostate cancers (PCA) frequently arise in the peripheral posterior zone of the gland and therefore adjacent to the rectum. Treatment can include brachytherapy and/or radiotherapy (RT); however, rectal toxicity can complicate therapy. A dilemma therefore arises in the balance between radiation dose and rectal adverse effects. Methods: Starting February 2012, until now 37 patients were included in this investigation. Under ultrasound guidance, a synthetic hydrogel (SpaceOAR) was injected between the prostate and the rectum, thus moving the rectum away from the high radiation dose volume, allowing dose escalation. The procedure was carried out in general anaesthesia and required approx. 10 min. The prescribed dose for the prostate was 80.0 Gy in 40 fractions. In 20 patients also the pelvic lymph nodes were irradiated with 50.4 Gy. IMRT planning was realized with and without hydrogel. During the treatment and 3 months after treatment acute toxicity was documented by the use of common toxicity criteria version 3.0. Results: So far median follow up time post hydrogel injection for all patients is 6 months. No acute toxicity for the hydrogel-application was observed. In the middle plane of the gland, the space between rectal wall and prostate could be increased by an average of 1.34cm. The mean V70 with hydrogel was 1.6% (range 0-8%) and without hydrogel 17.3% (range 8- 42%) resulting in a mean reduction of V70 of 90,9%. Until now 24 patients finished RT. 14 of these patients showed gastrointestinal toxicity (GIT) grade 1. No grade 2. GIT was observed. 13 patients reached the first follow up 3 months after RT. Only 2 of these patients showed GIT grade 1. No GIT grade 2 was described. Conclusions: Injected liquid to solid inert substance for prostate-rectum separation appears to be safe. Reducing rectal irradiation doses has the potential to lower rates of rectal toxicity and therefore improving QOL in men receiving RT for prostate cancer. More research is needed before conclusions can be reached as to the technology’s potential place in therapy.