tbuckley/cabot-search huggingface dataset:
Retrospective study of CT-guided radiofrequency ablation and laparoscopic radiofrequency ablation in the treatment of recurrent small hepatocellular carcinoma against the diaphragmatic dome.
Authors: Qin Zheng, Huaiyin Ding, Chuandong Zhu, Lixue Wang, Yuan Wan
Journal: Journal of Clinical Oncology (2017)

272 Background: Radiofrequency ablation (RFA) have been used to treat hepatocellular carcinoma (HCC) in the subphrenic area. Very few studies focus on ablation of recurrent small HCC against the diaphragmatic dome. The therapeutic safety, efficacy, and hospital fee have never been compared between CT guided RFA and laparoscopic RFA (L-RFA) either. Methods: CT guided RFA and L-RFA were performed in totally 116 patients with 151 local recurrent HCC lesions abutting the diaphragm. We compared major and minor postoperative complications, hospital stay and fee, overall survival (OS), and local tumor progression (LTP) between two groups for evaluating respective therapeutic efficacy and safety. Moreover, in CT-guided percutaneous RFA group, depending on the locations of recurrent HCC nodules differentiated puncture paths and ablation methods were used, and intraoperative complications were recorded. Results: There is no significant difference in OS and LTP between CT- guided RFA and LRFA.In recorded postoperative complications, the morbidity in CT-guided RFA group is lower than that of L-RFA group. The average safety margin is 8 and 11 mm in CT-guided RFA and LRFA group, respectively. The shoulder and back pain is significantly high in L-RFA group probably due to pneumoperitoneum. Moreover, overall hospital stay and cost is also lower in CT-guided RFA group. Conclusions: Both CT-guided RFA and L-RFA are considered to be an effective approach for recurrent small HCC abutting diaphragm. Particularly, CT-guided RFA is an easy and economic with less complications if suitable puncture paths and ablation methods can be applied.
The impact of extended lymph node dissection versus neoadjuvant therapy with limited lymph node dissection on biochemical recurrence in high-risk prostate cancer patients treated with radical prostatectomy: A multi-institutional analysis.
Authors: Takuya Koie, Teppei Ookubo, Koji Mitsuzuka, Shintaro Narita, Takamitsu Inoue, Sadafumi Kawamura, Tatsuo Tochigi, Tomonori Habuchi, Yoichi Arai, Chikara Ohyama, Takahiro Yoneyama
Journal: Journal of Clinical Oncology (2017)

e543 Background: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low-dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). The aim of this study was to assess whether neoadjuvant LHRH+EMP confers an oncological benefit for high-risk Pca compared to extended lymph node dissection (e-PLND). Methods: The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at 4 institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The neoadjuvant LHRH+EMP therapy included the administration of 280 mg/day of LHRH and EMP for 6 months before RP. The outcome measure was BRFS. Results: The 5-year BRFS rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9% and 54.7%, respectively ( P &lt; 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Conclusions: Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP might reduce the risk of biochemical recurrence.
Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC
Authors: Imane Chaib, Niki Karachaliou, Sara Pilotto, Jordi Codony Servat, Xueting Cai, Xuefei Li, Ana Drozdowskyj, Carles Codony Servat, Jie Yang, Chunping Hu, Andres Felipe Cardona, Guillermo Lopez Vivanco, Alain Vergnenegre, Jose Miguel Sanchez, Mariano Provencio, Filippo de Marinis, Antonio Passaro, Enric Carcereny, Noemi Reguart, Charo Garcia Campelo, Cristina Teixido, Isabella Sperduti, Sonia Rodriguez, Chiara Lazzari, Alberto Verlicchi, Itziar de Aguirre, Cristina Queralt, Jia Wei, Roger Estrada, Raimon Puig de la Bellacasa, Jose Luis Ramirez, Kirstine Jacobsen, Henrik J. Ditzel, Mariacarmela Santarpia, Santiago Viteri, Miguel Angel Molina, Caicun Zhou, Peng Cao, Patrick C. Ma, Trever G. Bivona, Rafael Rosell
Journal: JNCI Journal of the National Cancer Institute (2017)

The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non–small cell lung cancer (NSCLC) is limited by adaptive activation of cell survival signals. We hypothesized that both signal transducer and activator of transcription 3 (STAT3) and Src-YES-associated protein 1 (YAP1) signaling are dually activated during EGFR TKI treatment to limit therapeutic response. We used MTT and clonogenic assays, immunoblotting, and quantitative polymerase chain reaction to evaluate the efficacy of EGFR TKI alone and in combination with STAT3 and Src inhibition in three EGFR-mutant NSCLC cell lines. The Chou-Talalay method was used for the quantitative determination of drug interaction. We examined tumor growth inhibition in one EGFR-mutant NSCLC xenograft model (n = 4 mice per group). STAT3 and YAP1 expression was evaluated in tumors from 119 EGFR-mutant NSCLC patients (64 in an initial cohort and 55 in a validation cohort) by quantitative polymerase chain reaction. Kaplan-Meier and Cox regression analyses were used to assess the correlation between survival and gene expression. All statistical tests were two-sided. We discovered that lung cancer cells survive initial EGFR inhibitor treatment through activation of not only STAT3 but also Src-YAP1 signaling. Cotargeting EGFR, STAT3, and Src was synergistic in two EGFR-mutant NSCLC cell lines with a combination index of 0.59 (95% confidence interval [CI] = 0.54 to 0.63) for the PC-9 and 0.59 (95% CI = 0.54 to 0.63) for the H1975 cell line. High expression of STAT3 or YAP1 predicted worse progression-free survival (hazard ratio [HR] = 3.02, 95% CI = 1.54 to 5.93, P = .001, and HR = 2.57, 95% CI = 1.30 to 5.09, P = .007, respectively) in an initial cohort of 64 EGFR-mutant NSCLC patients treated with firstline EGFR TKIs. Similar results were observed in a validation cohort. Our study uncovers a coordinated signaling network centered on both STAT3 and Src-YAP signaling that limits targeted therapy response in lung cancer and identifies an unforeseen rational upfront polytherapy strategy to minimize residual disease and enhance clinical outcomes.
Preoperative radiotherapy (preop RT) in rectal cancer: Impact of chemotherapy on the outcome—Long-term results of the randomized 22,921 phase III trial of EORTC.
Authors: Jean Francois Bosset, Gilles Calais, Laurent Mineur, Philippe Maingon, Ljiljana Radosevic-Jelic, Alain Daban, Etienne Bardet, Alexander Beny, Jean Claude Ollier, Michel Bolla, Dominique Marchal, Jean Luc VAN Laethem, Vincent Klein, Jordi Giralt, Pierre Clavere, Pascal Cellier, Laurence Collette
Journal: Journal of Clinical Oncology (2013)

3560 Background: This 2x2 factorial design clinical trial evaluated the addition of Fluorouracil-based chemotherapy (CT) to preop RT and the use of adjuvant CT in patients with resectable T3-T4 M0 rectal cancer. The 5-year results showed that adding CT preoperatively or postoperatively had no significant effect on overall survival (OS) nor on disease-free survival (DFS) but a divergence seemed to emerge respectively at 2 and 5 years in the postop CT group. We report results with a median of 10.4 years. Methods: A total of 1011 patients were allocated in four treatment arms: preop RT ; preop RT + 2 CT courses ; preop RT + 4 postop CT courses ; preop RT-CT + postop CT. Preop RT was 45 Gy over 5 weeks. A one 5-day course of CT consisted of 5-Fu 350 mg/m²/d and Leucovorin 20 mg/m²/d. The effect of preop CT and adjuvant CT on OS and DFS was assessed by Logrank test (2-sided 5% significance level) stratified respectively for postop and for preop treatment. Written informed consent was obtained from all patients before randomization. Results: There is no significant difference in OS, nor in DFS between the groups receiving preop CT or not (p = 0.91 and p = 0.38 respectively). There is no significant difference in OS nor in DFS between the groups treated by postop CT or not (p = 0.32 and p = 0.29 respectively). The 10-year cumulative incidence of local recurrences is ~9 % in all the CT groups and 17.4 % in the preop RT alone group (p = 0.0044). The 10 year cumulative incidence of distant metastases (DM) is ~35 % in all treatment groups. Conclusions: With more that 10-years follow-up there is no benefit in rectal cancer by adding Fluorouracil-based chemotherapy preoperatively nor postoperatively to preop RT in terms of OS, DFS, nor in term of DM. Clinical trial information: 00002523.
Identifying characteristics of women cancer survivors with a recent history of falls.
Authors: Kerri M. Winters-Stone, Thais Reis, Sydnee Stoyles, Nathan Dieckmann
Journal: Journal of Clinical Oncology (2017)

113 Background: Epidemiologic data suggest that fall rates are increased among women with a history of cancer compared to women never diagnosed with cancer. However, the unique characteristics of women cancer survivors who fall are not completely understood. Our study aimed to identify the demographic, clinical and physical attributes of women treated for cancer and who experienced falling in the past year. Methods: Secondary data analysis of baseline data from aging women cancer survivors (greater than 50 years of age) about to participate in clinical exercise trials (n = 611). Based on self-report of having fallen in the last year (yes/no), women were compared on the following: age, cancer type (breast vs. other), cancer stage, time since diagnosis, presence of neuropathy or pain, comorbidities, BMI, physical activity, maximal leg press strength, chair stand time, walk speed, gait patterns, and the short physical performance battery (sPPB). Stepwise regression was run to determine attributes significantly associated with fall history. Results: 28% of women reported falling in the last year (n = 173) and 79% of fallers experienced a related injury. Women cancer survivors who fell were significantly more likely than women who did not fall to have: not received chemotherapy (25% vs. 13%), higher morbidity scores (2.2 vs. 1.8), higher BMI (30.6 vs. 29.2 kg/m 2 ), more neuropathy (49 vs. 39%), wider base of support (10.0 vs. 8.8 cm), more of the gait cycle spent in the stance phase (64 vs. 63%), longer chair stand times (12.8 vs. 11.9 sec.), and lower PPB scores (10.3 vs. 10.8). In stepwise regression models, receipt of chemotherapy, comorbidities, maximal leg strength, neuropathy, base of support, and % time in the stance phase of gait were significantly associated with the odds of having fallen in the last year. Conclusions: Women cancer survivors over 50 years old have a prevalence of falls approaching the 33% reported by the general population of women over 65; however, the rate of injurious falls is much higher in our sample of women cancer survivors. Fall prevention should be considered in women cancer survivors at an earlier age than usual for older women, particularly for survivors at higher risk for falls, and focus on exercise to improve gait and leg strength.
Dendritic cells generated with PDL-1 checkpoint blockade for treatment of advanced pancreatic cancer.
Authors: Jan Nesselhut, Dagmar Marx, Nicole Cillien, Hans Lange, Goncalo Regalo, Michael Herrmann, Timo Hupfeld, Raymond Y. Chang, Thomas Nesselhut
Journal: Journal of Clinical Oncology (2015)

4128 Background: The efficacy of immunotherapy with monocyte derived dendritic cells (MoDC) is controlled via immune checkpoints, among them the PD-1/PDL-1 pathway. PDL-1 expressed on DC delivers an inhibitory signal to T-cells upon binding to PD-1 expressed on activated T-cells. Blocking of PDL-1 on DC may lead to improved efficacy of DC therapy for pancreatic cancer. Methods: After isolating monocytes from peripheral blood of n = 44 patients with stage IV pancreatic cancer, who failed first-line chemotherapy, antigen primed MoDC were generated using standard protocols. Patients included in the follow-up analysis received a minimum of 3 vaccines. 10 patients received MoDC modified by PDL-1 blockade after failure of previous DC therapy. PDL-1 blockade was performed by adding soluble CD80 or anti-PDL-1 to MoDC. Cytokine release and T-cell activity were measured exemplary using a mixed lymphocyte culture (MLC). Results: Median survival after onset of DC-therapy was 8 months with MoDC alone (18 months after primary diagnosis) with longest follow up of 36 months (49 months after primary diagnosis). We could induce a secondary stabilisation (4 to 8 months) in 5 from 10 patients, who failed to respond to previous DC therapy by using MoDC modified by PDL-1 blockade. Cytokine measurement using MLC, which was exemplarily performed, shows a change in the cytokine release upon PDL-1 blockade. Conclusions: An effective immune response requires both the inhibition of inhibitory signals and the activation of an antigen specific T-cell response. The efficacy of dendritic-cell based therapy may be improved by blockade of PDL-1 on dendritic cells to avoid an inhibitory signal and thus improve the T-cell specific response. Further investigations are necessary to ascertain whether the combination of systemic anti PD1-therapy with DC therapy using MoDC modified with PDL-1 blockade may further enhance therapeutic efficacy in solid tumors.
Comparing study of positron emission tomography and ultrasonography in the detection of axillary lymph node metastasis in patients with early stage breast cancer
Authors: B. Song, J. Bae, J. Kim, H. Jeon, S. Jung
Journal: Journal of Clinical Oncology (2007)

616 Background: The current status of axillary lymph node is the most important prognostic factor in breast cancer. Axillary lymph node dissection (ALND) is currently the standard option for assessment of axillary lymph nodes. Positron emission tomography - computerized tomography (PET-CT) imaging and breast sonography are a noninvasive imaging modality that can detect malignant lymph node. The purpose of this study was to evaluate the clinical usefulness of axillary lymph node staging by means of PET-CT imaging compare with breast sonography in breast cancer. Methods: This study involves 129 breast cancer patients and clinically negative axillary node. All patients had whole body PET-CT imaging and breast sonography before SLN biopsy. After SLN biopsy, all patients underwent complete ALND. Axillary lymph nodes were evaluated by standard hematoxylin and eosin staining techniques, while sentinel nodes were further examined for micrometastatic disease. The findings of PET-CT imaging and breast sonography of 129 patients were compared with pathologic findings after operation. Diagnostic accuracy was evaluated applying ROC curve areas. Results: The sensitivity of PET-CT imaging was 60.0%; specificity and accuracy were 83.6% and 73.4%, respectively. The sensitivity, specificity and accuracy of breast sonography were 61.8%, 89.0%, and 77.3% respectively. The SUVs of axillary lymph node ranged from 0.0 to 7.01. Analysis using ROC curves revealed the area under each curve which indicated a diagnostic accuracy. For involvement of axillary lymph node, PET-CT imaging had the area under the curve of 0.735, breast sonography one of 0.769. Conclusions: Axillary lymph node staging using PET-CT imaging is inferior to the breast sonography in early stage of breast cancer patients. Our study reveals the value of PET-CT imaging is not good compare to the breast sonography in the detection of axillary lymph nodes metastasis in patients with early breast cancer. No significant financial relationships to disclose.
Quantitative Pericardial Delayed Hyperenhancement Informs Clinical Course in Recurrent Pericarditis
Authors: Arnav Kumar, Kimi Sato, Edlira Yzeiraj, Jorge Betancor, Lin Lin, Balaji K. Tamarappoo, Deborah H. Kwon, Rory Hachamovitch, Allan L. Klein
Journal: JACC. Cardiovascular imaging (2017)
S6K1 Regulates Self-Renewal of Leukemia Initiating Cells and Normal Hematopoietic Stem Cells
Authors: Joydeep Ghosh, Anindya Chatterjee, Baskar Ramdas, Michihiro Kobayashi, Peilin Ma, Yan Liu, David Plas, Reuben Kapur
Journal: Blood (2015)
Representation of peritoneal metastases in published clinical trials of metastatic colorectal cancer.
Authors: Jennifer Tseng, Darren S Bryan, Elizabeth Poli, Manish Sharma, Blase N. Polite, Kiran Turaga
Journal: Journal of Clinical Oncology (2017)

725 Background: Peritoneal metastases occur in 6-15% of patients with metastatic colorectal cancer. Non-invasive detection of peritoneal metastases is difficult given limitations in discrimination of cross sectional imaging. We hypothesized that patients with peritoneal metastases are underrepresented in clinical trials. Methods: Randomized controlled trials of systemic chemotherapy for metastatic colorectal cancer between 2003-16 were included after a PubMed search. Articles were restricted to those published in leading oncology journals and with ≥100 patients (total). Protocol designs were hand searched to identify whether clinical trials explicitly included or reported on patients with peritoneal metastases. Results: Of 72 clinical trials identified, 7 (10%) studies specifically reported inclusion of peritoneal disease (Table 1). Of 45,783 patients enrolled in all trials, 670 patients (1.5%) specifically had peritoneal metastases. Response for peritoneal disease was measured using Response Evaluation Criteria in Solid Tumors (RECIST) criteria in 6 (of 7, 86%) and modified World Health Organization (WHO) criteria in 1 but not reported in the final manuscript or supplementary material. Peritoneal specific outcomes were not reported in any study. No studies included metastatic colorectal cancer patients with peritoneal metastases alone. Conclusions: Patients with peritoneal metastases are underrepresented in published clinical trials. Specific efforts to include patients, measure burden of disease and response to therapy and report peritoneal specific outcomes are essential to draw generalizable inferences. [Table: see text]
Beyond Genomic Association: Ethical Implications of Elucidating Disease Mechanisms and Genotype-Influenced Treatment Response
Authors: John Noel M. Viaña, Roemel Jeusep Bueno, Frederic Gilbert
Journal: The American Journal of Bioethics (2017)

Kong, Dunn, and Parker (2017) highlight several ethical issues associated with the translation of genomic research findings into public health and clinical contexts. Among the ethical concerns they...
Perioperative outcomes of induction therapy followed by esophagectomy versus esophagectomy alone for treatment of esophageal cancer.
Authors: Cristina M. Merkhofer, Sam Joseph Lubner, Tracey Weigel, James D. Maloney, Traci Bretl, Ryan A. Macke, Justin D. Blasberg, Noelle K. LoConte, Mark A. Ritter
Journal: Journal of Clinical Oncology (2014)

e15017 Background: Induction chemoradiation therapy (CRT) followed by esophagectomy has recently gained wider acceptance as the preferred treatment for locoregionally advanced esophageal cancer. However, CRT has the potential to further debilitate patients and may complicate resection given the resulting inflammation and fibrosis that occurs in the surgical field. Controversy exists as to whether or not these potential effects have a negative impact on perioperative outcomes. Methods: We performed a retrospective review of 163 patients treated for primary esophageal cancer with potentially curative esophagectomy between January 2009 and June 2013 at our institution. Data including preoperative patient characteristics and perioperative outcomes was obtained from our prospectively collected and maintained database. Comparisons were made between patients who received induction therapy followed by surgery (n = 90) and surgery alone (n = 73). Results: All but two patients in the induction cohort received combined CRT. Induction therapy was successfully completed in 83 patients (92%). Preoperative characteristics varied significantly between cohorts, including age, nutritional status, and cardiovascular comorbidity. In comparing CRT plus surgery vs. surgery alone, no significant differences were noted in overall morbidity (39% vs. 52%, p=0.114), pulmonary complications (14% vs. 22%, p=0.225), or anastomotic leak rate (14% vs. 10%, p=0.473). Thirty-day (1% vs. 3%, p=0.587) and 90-day mortality (4% vs. 3%, p=0.692) were similar. In the CRT group, 25 patients (28%) had a pathologic complete response. Shorter mean LOS (9 days vs. 12 days, p=0.079) and more frequent discharge to home (96% vs. 83%, p=0.015) favored the induction cohort. Conclusions: Morbidity and mortality was similar in patients who did or did not receive CRT prior to esophagectomy in the present series. Patients in the CRT cohort were discharged home more often and a trend toward shorter LOS was noted. However, these patients tended to be younger and in better health prior to treatment. This study supports the hypothesis that induction CRT does not worsen perioperative outcomes in properly selected patients.
Preliminary analysis of biomarkers in plasma by SELDI to predict the response to EGFR tyrosine kinase inhibitors (TKIs) in NSCLC patients
Authors: L. Zhang, L. Ning, X. Zhang, Z. Q. Pan, X. Wang, F. Xu, Z. Z. Guan
Journal: Journal of Clinical Oncology (2006)

7189 Background: The identification of NSCLC patients who are most likely to respond to EGFR tyrosine kinase inhibitors (TKIs) have been investigated intensively. Although screenings for EGFR mutation and gene copy number are promising, these tests are not yet widely available. New predictor markers are urgently needed. The objective of this study was to identify proteomic markers in plasma to predict benefits for patients treated with EGFR TKIs. Methods: Proteomic spectra derived from plasma samples from EGFR TKIs-responsive patients and non-responsive patients were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). These proteomic spectra (WCX2 chips, Ciphergen Biosystems, Inc.) were then analyzed by comparing protein profiles in different response groups (PR Vs PD, training set). Another group of patients treaded with EGFR TKIs will be serving as testing set to validate the result of training set. Results: Totally, fifty-four advanced NSCLC patients were included in this study. All patients were treated with single agent of gefitinib or erlotinib. Twenty-nine patients were included in training set of this study. All were suitable for response evaluation. Ten patients (34.5%) were PR, 8 (27.6%) were SD, and 11 (37.9%) were progressive disease (PD). Total six significant protein peaks were significant (m/z 4288, 4595, 9191, 9349, 9397, and 9563) between PR group and PD group (table). Another twenty-five patients were included for testing set. Analyzing of testing set is still going on. Table shows PR and PD patients’ plasma comparison on WCX2 chips. Conclusions: This preliminary “training” set of spectra that uses SELDI-TOF MS technology found that six protein peaks seemed to be very important biomarkers to predict the response to gefitinib. Prospective tests to confirm these proteins and peptides will be present at this meeting. These results are promising for identifying new biomarkers of EGFR TKIs with SELDI. [Table: see text] No significant financial relationships to disclose.