tbuckley/cabot-search huggingface dataset:
Association between <i>ERCC1</i> and <i>XPA</i> expression and polymorphisms and the response to cisplatin in patients with non-seminomatous testicular germ cell tumors.
Authors: Julia Mendoza, Jorge Martinez-Cedillo, Carlos Alberto Hernández, Delia Pérez-Montiel, Clementina Castro, Eunice Fabián-Morales, Miguel Santibañez, Rodrigo González-Barrios, José Díaz-Chávez, Marco Alonso Andonegui, Luis F. Onate-Ocana, Miguel Jimenez, Nancy Reynoso, Marlene Núñez, Richard Dyer, Luis A. Herrera
Journal: Journal of Clinical Oncology (2013)

4555 Background: Cisplatin-based chemotherapy cures over 80% of testicular germ cell tumors (TGCTs); nucleotide-excision repair (NER) modifies the sensitivity to cisplatin. In this work we explored the association between NER-proteins and their polymorphisms (SNPs) with cisplatin-sensitivity (CPS) and overall survival (OS) of patients with advanced non-seminomatous (ns)-TGCTs treated with bleomycin-etoposide-cisplatin (BEP). Methods: ERCC1, XPA-expression and gammaH2AX-presence, were tested in cisplatin-treated cancer cell lines. ERCC1 and XPA-expression were also analyzed in ns-TGCTs by qPCR. Immunohistochemistry was performed to detect ERCC1 protein in ns-TGCTs specimens. The SNPs were genotyped by PCR-RFLPs technique. Results: High basal ERCC1-expression was observed in non-CPS cancer cell lines; ERCC1-expression augmented further, as well as gammaH2AX, after cisplatin-treatment. Basal ERCC1 expression increases in the non-CPS patients in Mexican and Peruvian populations compared to CPS patients (p&lt;0.001; p=0.002). XPAexpression levels weren’t different. These polymorphisms weren’t associated with CPS or OS. ERCC1-positive immunostaining was observed in 30/108 patients (27.8%). From 76 patients that were CPS, 59 (77.6%) were ERCC1-negative, compared with 17 (22.4%) that were ERCC1-positive (p=0.05). 5-year OS probability was smaller for those patients ERCC1-positive and non-CPS (15.38%) than tumor ERCC1-negative and CPS (89.3%) (p&lt;0.001). Using the Cox Model, adjusted on the prognosis groups, the hazard ratio (HR) of death in patients with ERCC1-negative and non-CPS was &gt;14.43 and in patients ERCC1-positive and non-CPS the HR was &gt;11.86 (p&lt;0.001). Conclusions: High-levels of ERCC1-expression and ERCC1-protein are associated with non-CPS, suggesting the use of ERCC1 as a potential indicator of response to cisplatin-based chemotherapy and the prognosis in patients with ns-TGCTs. Moreover, it’s important to identify patients potentially non-CPS in order to diminish the toxicity of cisplatin and improved quality of life avoiding adverse effects due to this agent. Work supported by CONACYT 83959 and PAPIIT IN213311-3.
There is more: Intrasexual competitiveness, physical dominance, and intrasexual collaboration
Authors: Abraham P. Buunk
Journal: Behavioral and Brain Sciences (2017)

Abstract It is emphasized that in organizational settings, the responses to same-sex attractive others are enhanced among individuals high in intrasexual competitiveness; that especially attractive rivals who are perceived as unfriendly will induce competition; that among males, physical dominance may induce more competition than physical attractiveness; and that especially males may prefer to associate with attractive same-sex others for intrasexual collaboration.
Coexisting KRAS and PIK3CA exon 20 mutations as a potential poor-prognosis factor in metastatic colorectal cancer (mCRC).
Authors: Maria Elena Elez Fernandez, Guillem Argiles, Judit Matito, Leire Mendizabal, Debora Moreno, Jose Jimenez, Javier Hernandez-Losa, Teresa Macarulla, Jaume Capdevila, Maria Alsina, Tamara Sauri, Analia Azaro, Cristina Cruz Zambrano, Stefania Landolfi, Enrique Sanz, Santiago Ramon y Cajal, Paolo Nuciforo, Jordi Rodon, Josep Tabernero, Ana Vivancos
Journal: Journal of Clinical Oncology (2014)

3591 Background: Molecular screening and biomarker enrichment strategies in mCRC clinical trials have demonstrated to have an impact in treatment benefit and prognosis. The data obtained from these strategies progressively incorporated in routine clinical practice, may lead to the obtention of relevant information to optimize treatment decisions. Methods: From 01/2011 to 12/2013, 415 patients (pts) with advanced chemorefractory mCRC underwent genetic tumor profiling as part of Vall d’Hebron University Hospital Phase I Trial Molecular Prescreening Program. Mutation (MT) profiling was performed by single-base extension chemistry followed by mass detection (MassARRAY, Sequenom) including 268 frequent hotspots in 25 oncogenes, among them, KRAS, BRAF, NRAS, and PIK3CA. Results: We found a KRAS MT incidence of 48% (199/415 pts), slightly above other reported studies. The PIK3CA, BRAF and NRAS MT rates were 14% (58/415), 6.5% (27/415) and 3% (12/415) respectively. Coexisting KRAS and PIK3CA MT were found in 44 out of 199 pts (22.1%). PIK3CA MT were more frequently detected in the helical domain (HD, exon 9) than in the kinase domain (KD, exon 20). Among KRAS wild type (WT) pts, HD vs. KD MT were detected at approximately a 2:1 ratio (8 HD, 4 KD), consistent with previous reports. Interestingly, in the KRAS MT background, the ratio of MT in HD vs. KD in PIK3CA was dramatically increased in our population with a 14:1 ratio (41 HD, 3 KD). Upon dissecting the KRAS MT group, we found G13D MT to show a very low coexistence with PIK3CA MT (3/36 pts, 8%) in contrast to other series in less heavily pretreated populations. Conclusions: This study represents a thorough profiling of frequent oncogene MT in mCRC. Our analysis shows that certain profiles such as coexisting KRAS and PIK3CA-KD MT or KRAS G13D and PIK3CA MT seem to be underrepresented in our heavily pretreated population. Therefore, these findings suggest that both groups would be of particular poor prognosis. Nevertheless, this observation must be confirmed in larger and prospective series representing overall mCRC population.
Perceptions versus interpretations, and domains for self-fulfilling prophesies
Authors: Jennifer Church
Journal: Behavioral and Brain Sciences (2017)

I suggest two ways in which Jussim's extensive discussion (in his 2012 book) could be enriched: first, by exploring the distinction between perceptual judgments and interpretive judgments; second, by considering the power of expectations to be self-fulfilling in the case of young children and the case of fragile egos.
Modulation of breast cancer cell-free DNA with surgical resection.
Authors: Howard B. Urnovitz, Julia Beck, Ekkehard Schütz, Gopal Singh, William M. Mitchell, Dalliah M. Black, Gildy Babiera, Isabelle Bedrosian, Henry Mark Kuerer, Gordon B. Mills, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2013)

11060 Background: Recently we demonstrated the ability to detect the presence of invasive breast cancer by next generation sequence (NGS) analysis of cell-free DNA (cfDNA) in serum without prior knowledge of the specific gene perturbations of the neoplasm (J. Clin. Oncology 2010; 28 (15S):10505). We hypothesized that cfDNA levels would hold promise as a marker to monitor therapeutic efficacy in breast cancer. In this study, we sought to determine whether cfDNA decreases after surgery in patients with operable invasive breast cancer. Methods: Serum was collected before and 1-4 weeks after surgery from 16 breast cancer patients and also from 24 age and gender matched controls. cfDNA was isolated from the serum, amplified by Chronix proprietary method and sequenced on an Illumina HiSeq platform. The breast cancer derived cfDNA sequences from each patient were compartmentalized in 250kbp bins, normalized, and compared to the mean (+/- 3SD) of the controls to identify regions of chromosomal number imbalance (CNI). Genomic DNA was isolated from the primary tumor and blood WBC buffy coat, pre-amplified, sequenced and subjected to comparative analysis with cfDNA. Results: Analysis of pre- and post surgery serum demonstrate that CNIs are present in the pre-surgery serum cfDNA that correlated with the associated tumor CNI and was not observed in WBC genomic DNA. The number of tumor associated CNI DNA biomarkers ranged from as low as 3 to as high as 865. In 13 of 16 patients (81%) analyzed, the post-surgery cfDNA was free of detectable tumor related-CNI DNA. In the remaining 3 patients, only a partial reduction in tumor specific CNI DNA serum biomarkers was observed, since some markers were still detectable after surgery. Conclusions: cfDNA from primary breast carcinomas accurately reflects tumor CNI. Removal of the primary tumor results in the elimination of tumor cfDNA in the majority of patients. Thus cfDNA may be of clinical value in evaluation of therapeutic efficacy on a real time basis. Further work is needed to determine if residual tumor CNI in cfDNA after surgery is a marker of minimal residual disease which can be pursued as a prognostic marker.
A protocol with adjuvant chemotherapy (CT) and radiotherapy (RT) for endometrial cancer: Results.
Authors: Margarita Romeo, Laia Capdevila, Sara Cros, Antoni Tarrats, Maya Takeuchi, Juan Jose Torrent, Elvira Carballas, Josep Maria Sastre, Maria Carmen Gomez, Victoria Tuset, Gustavo Tapia, Carmen Balana
Journal: Journal of Clinical Oncology (2013)

e16549 Background: The classic adjuvant treatment for high-risk endometrial cancer is RT. Several phase III trials explored the role of CT, as single treatment or added to RT sequentially (ST) or concurrently (CR), but design heterogeneity hampers conclusions. We report the results of a single-institution protocol with adjuvant CT + RT for advanced stages or type II histologies. Key points: (1) ST and CR permitted. (2) CT used pre-, post- and/or during RT: carboplatin AUC 5 + paclitaxel 175 mg/m2 (150 during RT) Q3W, 4-6 cycles (“carbotaxol”). (3) since 2010, cisplatin 50 mg/m2 was used for CR (on day 1 and 28 of RT). CR was preceded/followed by carbotaxol. Methods: All patients (PT) included in the protocol between 1/2005 and 9/2011 were retrospectively revised. Endpoints were survival and toxicity grade 3-4. Kaplan Meier and Fisher test were used. Conclusions: CR-carbotaxol showed a longer progression-free and overall survival than ST without reaching statistical significance (log rank, p= 0.14 and p=0.33). Median survivals with CR-cisplatin were not reached because of shorter follow-up. Statistical differences in toxicities were not found. In the CR-carbotaxol arm, 5 PT had grade 3-4 acute diarrhoea vs none in the others. [Table: see text]
Retrospective cohort analysis of neoadjuvant treatment and survival in resectable and borderline resectable pancreatic ductal adenocarcinoma in a high-volume referral centre.
Authors: Malinda Itchins, Jennifer Arena, Joel Rabindran, Nahm Christopher, Sia Kim, Emma Gibbs, Anthony J. Gill, Richard Maher, Geoffrey Schembri, Elizabeth Bailey, Anubhav Mittal, Sarah Bergamin, Matthew Wong, George Hruby, Andrew Kneebone, Nick Pavlakis, Jaswinder S. Samra, Stephen Clarke
Journal: Journal of Clinical Oncology (2017)

395 Background: The 5 year (yr) overall survival (OS) of pancreas cancer (PC) is &lt; 5%. Surgical resection is the only curative treatment (tx), most relapse within 2yrs. Neoadjuvant (NA) tx can benefit by eradicating micro-metastases, avoids futile surgery if metastases develop, improves dose intensity and may down stage disease. Currently, there are no data that clearly demonstrate improved OS with NA tx. Randomised trials are in progress. Methods: A retrospective analysis of all patients (pts) who received NA therapy across campuses,in Sydney, was performed. Pt records were identified and all were discussed in a MDT by a panel of PC specialists. Results: 588 PC pts were treated between August 2011-July 2016. After consideration of anatomy, pt characteristics and preference 82 pts (14%) received NA tx, 30% were resected upfront. 26 pts were ‘borderline’ and received sequential chemo-radiotherapy (ctxRT). Median age at diagnosis (dx) was 73 yrs, 50% were men. Median follow up time was 31.2 months (m). 84% pts were resected. There was 1 death at 90 days. An R0 was achieved in 74%. A detailed tx overview will be provided. Most received gemcitabine/abraxane. For those who had PET, low SUV pre-operative correlated with high pathological regression score, 3 pts 0%. Median OS for all pts was 25.9 m (95% CI 21.2, 30.2). Survival by stage: 1- 21.2 mo (11.8, 29.5); 2- 25.2 m; stage 3-4 (not reached). Pts who received ctx alone OS 25.3mo (17.2,29.5); ctxRT 29.0 m (17.3, NA) (p = 0.03). R0 survival was 29.0 m (21.2, NA) and R1, 23 m. 30% were alive at 3 yrs. Time to recurrence was 22.3 m (14.3, NA). Weight &gt; 74kg was predictive of survival; OS 23.0 m v 29.5m (p = 0.002). There was a trend to survival benefit in females (p = 0.099) and baseline LDH &lt; 280 (IU/L) (p = 0.07). Age at dx, ECOG (0 v 1), baseline albumin, bilirubin, Ca 19.9, NLR ( &lt; 3.1) and CRP and stage at dx were not predictive of survival. Conclusions: This pt cohort demonstrates superior survival with NA therapy in selected pts across stages in a high volume multi-disciplinary PC centre. Outside a clinical trial, NA therapy is evolving to be our standard of care in fit pts with any degree of vessel involvement.
Association of baseline pro-inflammatory (IL-6, CRP) and coagulation (D-dimer) markers with relative dose intensity (RDI) in women with breast cancer (BC) undergoing (neo) adjuvant chemotherapy (chemo).
Authors: Yuan Yuan, Nilesh L. Vora, David D. Smith, Timothy W. Synold, Joanne E. Mortimer, Thehang H. Luu, George Somlo, James Ross Waisman, Joseph Chao, Abrahm Levi, Jennifer Choi, Vani Katheria, Vivi Tran, Shu Mi, Laura Zavala, Arti Hurria
Journal: Journal of Clinical Oncology (2015)

9539 Background: Chemo decreases the risk of relapse and mortality from BC. Chemo efficacy depends on RDI, and patients (pts) who receive <85% RDI have poorer overall survival. Pro-inflammatory and coagulation factors such as IL-6, CRP and D-dimer serve as biomarkers for aging. The utility of these markers as biologic correlates of the ability to deliver chemo (i.e. RDI) in pts with BC is unknown. This study was performed to determine if prechemo IL-6, CRP and D-dimer correlate with RDI in women with stage I-III BC requiring chemo. Methods: This is a prospective longitudinal study that enrolled 153 women with BC who had pre-chemo peripheral blood assayed for IL-6, CRP, and D-dimer. (Neo)Adjuvant chemo regimens were prescribed at the physician’s discretion. Univariate analyses evaluated the association of these 3 markers with <85% RDI and clinical factors (patient age, physician rated Karnofsky performance status (KPS) and number of co-morbidities). Multivariate analyses were performed to evaluate the association of each biomarker and clinical factor with RDI. Results: 153 pts (mean age of 56 y, range 30-81 y) with stage I-III BC (Stages I [23%], II [54%], III [24%]) were enrolled. Chemo regimens include: doxorubicin+cyclophosphamide /paclitaxel (AC-T: 44%), docetaxel+cyclophosphamide (TC: 35%), docetaxel/carboplatin/trastuzumab (TCH: 7%) and other regimen (14%). RDI was less than 85% for 26% of pts. There were associations between RDI <85% and higher D-dimer (p<0.01) and IL-6 (p=0.02) levels pre-chemo (Table 1). There was no association between RDI <85% and CRP or above clinical factors. Conclusions: Higher pre-chemo levels of IL-6 and D-dimer correlate with reduced RDI (<85%). Future studies are underway to validate these findings. Table 1. Association of pre-chemo biomarkers, clinical factors and RDI <85%. Clinical trial information: NCT01030250. Biomarkers/ Clinical factors OR (95%CI) p value D-dimer 2.47 (1.35-4.73) 0.01 CRP 1.00 (1.00-1.00) 0.82 IL6 1.10 (1.02-1.21) 0.02 Age 1.01 (0.95-1.06) 0.49 KPS 1.01 (0.98-1.04) 0.32 No. Comorbidities 0.97 (0.66-1.40) 0.33
Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy.
Authors: Seung Yeun Chung, Jee Suk Chang, Byung Min Lee, Kyong Joo Lee, Si Young Song, Jinsil Seong
Journal: Journal of Clinical Oncology (2017)

372 Background: In locally advanced pancreatic cancer, radiotherapy (RT) is an effective treatment modality, but challenged by conflicting results. Now, in the era of intensity-modulated radiation therapy (IMRT), dose escalation is possible without increasing the dose to organs-at-risk. We investigated whether RT dose escalation would improve treatment outcomes without increasing severe toxicity. Methods: From 2005 to 2015, a total of 497 locally advanced - including both borderline resectable and unresectable - pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy were included. A total of 281 (56.5%) patients received 3D conformal RT and 216 (43.5%) patients received IMRT. Most common dose scheme for IMRT was 58.42 Gy in 23 fractions (EQD2 61.05 Gy). Patients were divided into two groups; &lt; 61 Gy group (n = 345) and ≥ 61 Gy group (n = 152). Overall survival (OS), progression-free survival (PFS), local failure-free rate (LFFR), distant failure-free rate (DFFR) and toxicity rates were assessed. Results: At a median follow-up time of 14.1 months (range, 2.3-128.5 months), OS, PFS, LFFR, and DFFR rates were significantly higher in ≥ 61 Gy group. The 1-year OS rates were 74.7% and 60.6% (p = 0.001) and 1-year PFS rates were 46.2% and 30.9% (p &lt; 0.001), for ≥ 61 Gy and &lt; 61 Gy group, respectively. The 1-year LFFR was 86.9% and 70.9% (p = 0.001) and 1-year DFFR was 56.4% and 45.8% (p = 0.007), respectively. After multivariate analysis, ≥ 61 Gy group remained a favorable significant factor for OS (p = 0.019), PFS (p = 0.001), LFFR (p = 0.004), and DFFR (p = 0.008). When 152 patients in each group were matched by propensity score matching, ≥ 61 Gy group still showed higher OS (p = 0.011), PFS (p = 0.016), and LFFR (p = 0.002), but not DFFR (p = 0.205). There was no acute gastrointestinal toxicity higher than Grade 3 in both groups. Late toxicity rates were also similar, with RT-related duodenal and gastric hemorrhage ( ≥ Grade 3) in 19 patients (5.5%) in &lt; 61 Gy group and 7 patients (4.6%) in ≥ 61 Gy group. Conclusions: Patients who received higher RT dose showed not only improved PFS and LFFR but improved OS without an increase in severe toxicity. Dose escalation via IMRT is recommended for RT in locally advanced pancreatic cancer patients.
Modified Glasgow prognostic score as a selection marker for colorectal cancer patients with multiple metastases who can underwent primary site resection followed by multidisciplinary therapy.
Authors: Tadanobu Shimura, Yuji Toiyama, Susumu Saigusa, Hiroki Imaoka, Masato Okigami, Hiroyuki Fujikawa, Junichiro Hiro, Minako Kobayashi, Masaki Ohi, Toshimitsu Araki, Yasuhiro Inoue, Keiichi Uchida, Yasuhiko Mohri, Masato Kusunoki
Journal: Journal of Clinical Oncology (2017)

655 Background: We often encounter the colorectal cancer (CRC) patients with multiple distant metastases who rapidly progress after resection of primary tumor site due to preventing bowel obstruction, tumor bleeding and perforation. However, there has been few knowledge for identification of these patients at the present time. In this study, we evaluated the association between clinicopathological findings, including with preoperative laboratory data and survival outcome, and possibility of multimodality therapy in CRC patients with multiple metastases after resection of primary tumor lesion. Methods: Clinicopathological findings and preoperative laboratory data, including carcinoembryonic antigen (CEA) and systemic inflammatory response markers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and modified Glasgow Prognosis Score (mGPS) for 92 CRC patients with multiple metastases from 2005 to 2014 were collected. We performed multivariate analysis for overall survival (OS) in cox proportional hazard model. In addition, we performed multivariate logistic regression analysis to evaluate the factors influencing possibility of postoperative multimodality therapy. Results: Postoperative multimodality therapy improved overall survival significantly. Among serum markers, elevated CEA, NLR, and mGPS were significant indicators of poorer OS. Multivariate analysis for OS revealed that elevated CEA (P = 0.026), mGPS (P = 0.038), and undifferentiated histology type (P = 0.02) were independent poorer prognostic factors. In addition, multivariate logistic regression analysis showed that elevated mGPS (P = 0.029) and higher age (P = 0.013) were independent risk factors for difficulty of introducing postoperative multidisciplinary therapy. Conclusions: Preoperative mGPS is useful objective marker for selection of colorectal cancer patients with multiple metastases who can undergo primary resection followed by multidisciplinary therapy.
Recombinant adenoviral human p53 gene combined with radiotherapy in treatment-advanced sarcoma.
Authors: Jianhao Geng, Shaowen Xiao, Shenwen Zhang
Journal: Journal of Clinical Oncology (2013)

10557 Background: Advanced soft tissue sarcoma generally are resistant both chemo- and radiotherapy. P53 gene has multiple anti-tumor functions including sensitizing tumor cells to chemo- or radiotherapy. Methods: Thirty-six patients with advanced, unresectable soft tissue sarcoma, with an age of 48.3±19.1 years old, 19 males and 17 females, were treated with combination of p53 gene and radiotherapy. Recombinant adenoviral human p53 gene (rAd-p53) was given through intratumoral injection at a dose of 2 x 10 12 rAd-p53 viral particles (VP) once per week for 4-9 times. If tumors spread to the peritoneal cavity with or without malignant peritoneal effusions, 2 x 10 12 VP diluted into 500 ml of physiological saline was infused into abdominal cavity, once a week for 4 times. Intensity modulated radiation therapy were given at a total dose of 20 – 70 Gy in 2-7 weeks. Results: The overall response rate at 3 months after treatment was 44.4% (16/36, 2/36 in CR and 14/36 in PR). Twenty patients (55.5%) were stable. The tumor in two patients was successfully resected after the combined therapy. Medium overall survival and progress free survival time were 17.8 and 13.5 months, respectively. The survival rates of one year, two years three years, and 5 years were 58.3%, 25.0%, 13.9%, and 8.3%, respectively. Mild or medium fever was observed in all patients after application of rAd-p53. No serious adverse events or complications observed. Conclusions: Combination of local p53 gene and radio-therapy is effective and safe treatment regimen for advanced soft tissue sarcoma.