tbuckley/cabot-search huggingface dataset:
Effect of tissue ischemia on prostatic androgen levels.
Authors: M. C. Risk, E. A. Mostaghel, B. Marck, A. M. Matsumoto, P. Nelson, R. B. Montgomery, D. W. Lin
Journal: Journal of Clinical Oncology (2010)

4643 Background: Androgen concentrations sufficient to activate the androgen receptor (AR) a have been measured within the prostate and in tumor metastases from men with castration resistant prostate cancer. Methods of tissue collection may influence androgen levels. We sought to investigate the effect of tissue ischemia on concentration of androgens in prostatic tissue. Methods: Men undergoing radical prostatectomy for clinically localized prostate cancer underwent intraoperative and post-operative prostate tissue acquisition. Seven time points were collected for each patient. The first time point was at time of prostate exposure in the operative field, the second time point was immediately after the blood supply was clamped, the third time point was immediately after prostate removal, and subsequent time points were in 30-60 min increments following prostate removal. At each time point, prostate tissue was immediately flash-frozen in liquid nitrogen. Steroids were extracted from the tissue, and levels of dihydrotestosterone (DHT) and testosterone (T) were determined by mass spectrometry. Results: Mean initial DHT and T tissue concentrations prior to ischemia were 3.64 ± 1.60 pg/mg and 0.54 ± 1.43 pg/mg, respectively. There was greater core-to-core variability in the assay at smaller biopsy weights (≤ 3.5 mg), however this did not significantly limit the data. Tissue ischemia did not have a significant effect on DHT concentrations up to 3 hrs following vascular clamping. A decrease in T was found at the initial ischemic point (prostate removal), however levels of T were at the lower assay detection limit, and no further decrease in T was seen with up to 3hrs of tissue devascularization. Conclusions: Average intraprostatic DHT and T concentrations in noncastrate men with prostate cancer are similar to those found in other studies, demonstrating that prostate needle biopsies are a reliable method of tissue acquisition for this purpose. Ischemia did not have a significant effect on intraprostatic concentrations of DHT and T in our assay. These findings have implications on future studies utilizing prostatic tissue for steroid hormonal measurements, particularly if obtained after prolonged ischemia as found following laparoscopic/robotic prostatectomy. No significant financial relationships to disclose.
Accuracy of endorectal ultrasonography in evaluation of response to chemoradiation in locally advanced rectal cancer.
Authors: B. Farnault, L. Moureau-Zabotto, C. de Chaisemartin, M. Giovannini, G. Monges, J. Delpero, P. Viens, M. Resbeut
Journal: Journal of Clinical Oncology (2011)

3543
Predictive parameters of symptomatic haematochezia following 5-fraction gantry-based SABR in prostate cancer.
Authors: Hima Bindu Musunuru, Melanie Davidson, Patrick Cheung, William Chu, Hans T. Chung, Danny Vesprini, Stanley K. Liu, Alexandre Mamedov, Ananth Ravi, Laura D'Alimonte, Kristina Commissso, Joelle Antoine Helou, Andrea Deabreu, Liying Zhang, Andrew Loblaw
Journal: Journal of Clinical Oncology (2016)

79 Background: To identify clinical and dosimetric predictors of high-grade haematochezia (HH) following 5-fraction gantry based stereotactic ablative radiotherapy (SABR). Methods: Data about haematochezia in 258 patients who received 35-40Gy SABR in 5-fractions (weekly or alternate days) as part of sequential phase II prospective trials was retrieved. Haematochezia was graded as per the Fox Chase LENT criteria, ≥ grade 2 rectal bleeding was labeled as HH. Patients needing steroid suppositories, 4% formalin or 1-2 sessions of argon plasma coagulation (APC) were graded as grade 2 haematochezia. If a patient required &gt;2 sessions of APC, blood transfusion or a course of hyperbaric oxygen, this was grade 3 and development of visceral fistula was grade 4. Various dosimetric and clinical factors were analyzed using univariate and multivariate (MVA) analyses. Receiver-operating characteristic (ROC) curve analysis and recursive partitioning analysis (RPA) were used to determine clinically valid cut-off points and risk groups, respectively. Results: Median follow-up was 29.7 months (IQR 20.6, 61.7). HH was observed in 19.4%. Median time to develop HH was 11.7 months (IQR 9.0, 15.2). Resolution occurred a median of 6.7 months (IQR 5.7, 12.4) later; 3% was prevalent at last follow-up. At two years, cumulative HH was 4.9%, 27.2% and 42.1% in patients who received 35Gy to prostate (4mm planning target volume-PTV margin), 40Gy to prostate (5mm PTV margin) and 40Gy to prostate/seminal vesicles (5mm PTV margin), respectively ( p-value&lt; 0.0001). In the ROC analysis, volume of rectum receiving radiation dose of 38Gy (V38) was a strong predictor of HH with an AUC of 0.65. In MVA, rectal V38 (≥2.0cc; p-value&lt;0.0001, OR 4.9); use of anti-coagulants (p-value&lt;0.0002, OR 14.9) and presence of hemorrhoids (p-value&lt;0.006, OR 3.2) were the strongest predictors. In RPA, rectal V38&lt;2.0cc and use of anticoagulants orrectal V38 ≥2.0cc plus one other risk factor resulted in a HH risk&gt;30%. Conclusions: Rectal V38 and two clinical factors were strong predictors of high-grade haematochezia following 5-fraction SABR. Planning constraints should aim to keep the rectal V38 below 2.0cc.
Effect of Dioxin (TCDD) on Gene Transcription of Human CD34+ Hematopoietic Cells.
Authors: Nicola S. Fracchiolla, Federica Servida, Pier A. Bertazzi, Paolo Corradini, Antonio Colombi, Katia Todoerti, Luca Agnelli, Antonino Neri, Giorgio Lambertenghi Deliliers
Journal: Blood (2007)
The impact of clinical stage on renal cell carcinoma outcomes: Implications for neoadjuvant trial design.
Authors: Mark Wayne Ball, Michael A Gorin, Phillip M Pierorazio, Hans J. Hammers, Lauren Christine Harshman, Charles G. Drake, Mohamad E Allaf
Journal: Journal of Clinical Oncology (2015)

482 Background: Outcomes for patients with RCC are reported by pathologic stage; however, determination of therapy and patient counseling are based on clinical staging. Moreover, the development of neoadjuvant therapies that may requires knowledge of clinical stage-specific outcomes for trial design. Because of a paucity of reported outcomes, we characterized pathologic upstaging, recurrence-free survival (RFS) and cancer-specific survival (CSS) by stage at our institution. Methods: Our renal mass registry was queried for patients with localized RCC who underwent extirpative surgery with from 2003-2013 stratified by clinical stage. The proportion of cases upgraded by stage were determined. Survival outcomes were analyzed using the Kaplan-Meier method. Results: A total of 2,144 cases were captured during the study period. Median follow-up was 44.5 months. Clinical to pathologic upstaging is listed in the table. The highest degree of upstaging occured in cT2 cases, with 47% of cT2a and 48% of cT2b upstaged to ≥cT3a. RFS at 60 months for cT1a was 98.4%, cT1b 95.5%, cT2a 78.4%, cT2b 74.4%, cT3a 68.0%, cT3b 63.5%, cT3c 27.8%. CSS at 60 months for cT1a was 99.3%, cT1b 96.3%, cT2a 82.7%, cT2b 81.7%, cT3a 88.7%, cT3b 66.8%, and cT3c 76.9%. Harrell's C index for CSS was similar for both clinical (0.68) and pathologic stage (0.75). Conclusions: While the rate of upstaging increases markedly with increasing clinical stage, survival models based on clinical stage perform as well as those based on pathologic staging. The high rate of upstaging in cT2 disease supports enrollment of these patients in adjuvant clinical trials. Knowledge of these clinical stage-specific outcomes may be helpful for trial design. [Table: see text]
Mutations of the catalytic domain of PI3 kinase and correlation with clinical outcome in trastuzumab-treated metastatic breast cancer (MBC).
Authors: J. W. Cook, E. Paxinos, L. J. Goodman, S. M. Ali, K. Leitzel, W. Koestler, A. Rivera, J. M. Weidler, W. Huang, J. Sperinde, S. J. Williams, M. Bates, A. Lipton
Journal: Journal of Clinical Oncology (2011)

582 Background: Resistance to HER2 antagonism in HER2-positive breast cancer has been associated with activation of the PI3K signaling pathway. PIK3CA mutations in exon 9 and exon 20 have been shown to activate the AKT-mTOR pathway downstream of EGFR-family receptor tyrosine kinases, where most targeted drugs for breast cancer exert their effect. Methods: We measured PIK3CA mutation status in exons 9 (E545K and E542K) and 20 (H1047R) using two different methods [pyrosequencing (Monogram) and an allele-specific, real-time PCR assay (D×S)] and correlated the results with clinical outcomes in a cohort of patients (pts) with trastuzumab-treated MBC. Results: 22/85 pts (26%) with available FFPE tissue had mutations in exon 9 or exon 20. Results obtained by the two methods were 100% concordant. No statistically significant association was seen between the presence of PIK3CA mutations and the levels of HER2, HER3, or p95HER2, as measured by VeraTag™ (HERmark), although there was a trend favoring lower p95 levels in mutants (p=0.07). Including all pts, no differences were observed in either PFS (HR 1.23 for mutant vs. WT, p=0.47) or OS (HR 1.56, p=0.19). In HER2 FISH-positive pts (N=65), no differences were observed in either PFS (HR 1.72, p=0.15) or OS (HR 2.08, p=0.09). PIK3CA mutants fared better in the FISH-negative population (N=20) for PFS (HR 0.34, p=0.03) but not for OS (HR 0.74, p=0.6). Among pts that overexpressed HER2 protein (>13.8 by HERmark, N=59), those with exon 9 mutations, but not those with exon 20 mutations, experienced shorter PFS (HR 8.04, p=0.004 and HR 1.06, p=0.89, respectively) and OS (HR 4.85, p=0.03 and HR 1.48, p=0.45, respectively) when compared to PI3K WT pts. Conclusions: Exon 9 mutations appeared to exert a deleterious effect on outcomes, but exon 20 mutations did not. Pts with PIK3CA mutations, but without HER2 gene amplification, experienced better outcomes on trastuzumab treatment than PIK3CA WT pts, while no association was observed in HER2 amplified pts. These data are hypothesis-generating and require confirmation in larger controlled datasets of trastuzumab-treated MBC pts. Grant support from Komen for the Cure.
Impact on Pulmonary Function of Pre-Transplant Radiotherapy in Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplant (ASCT).
Authors: Christy Stotler, Paul Elson, Brian Bolwell, Matt Kalaycio, Brad Pohlman, Ronald Sobecks, Robert Dean, Steven Andresen, Edward Copelan, Josephine Chan, John Sweetenham
Journal: Blood (2008)
Marrow-Infiltrating T Cells In Patients with Chronic Lymphocytic Leukemia Display Markers of Functional Impairment and Express PD-1
Authors: Ursula Hainz, Quinlan L. Sievers, Kristen Stevenson, Natalie R. Goldstein, David Dorfman, Jennifer R Brown, Gordon J. Freeman, Catherine J Wu
Journal: Blood (2010)
Among men with low-grade prostate cancer on prostate biopsy, the 4Kscore to predict prostate cancer aggressiveness at prostatectomy.
Authors: Bruno Nahar, Sanoj Punnen, Stephen M Zappala, Daniel Sjoberg, Dipen Parekh
Journal: Journal of Clinical Oncology (2016)

65 Background: Most men diagnosed with prostate cancer in the United States have low-grade tumors. While many of these men are good candidates for active surveillance, a proportion will have a bad outcome due to the presence of a more aggressive prostate cancer that was missed on initial biopsy. A recent study confirmed the 4Kscore accurately predicts the likelihood of aggressive cancer on prostate biopsy. We analyzed if the 4Kscore could predict the presence of more significant cancer in men with low-grade tumors on the diagnostic biopsy. Methods: A recent prospective validation of the 4Kscore was conducted at 26 sites throughout the United States. We selected men who were found to have low-grade (Gleason 6) cancer on biopsy for this analysis. The 4Kscore calculates the risk of aggressive prostate cancer on prostate biopsy by a blood test that measures levels of four kallikrein biomarkers (total PSA, free PSA, intact PSA, and human kallikrein-2) plus age, DRE findings, and prior biopsy status. We investigated whether the 4Kscore was associated with more significant cancer among men found to have Gleason 6 cancer on prostate biopsy. We also looked at a subset of these men who underwent radical prostatectomy to see if the 4Kscore was associated with prostate cancer being upgraded in the surgical specimen. Results: Among the 1,312 men enrolled in this trial, 306 men were found to have Gleason 6 cancer on prostate biopsy. The 4Kscore was significantly associated with the number of positive cores (p=0.001) and the millimeters of cancer seen (p=0.0002), with higher 4Kscores relating to more extensive cancer present on biopsy. In the subpopulation of 51 men who underwent radical prostatectomy, the median 4Kscore was significantly higher among men who had an upgrade to Gleason 7 or higher [15% (8,25)] compared to men who did not experience an upgrade [7% (4,14)] (p=0.032) in their final pathology. Conclusions: Among men with Gleason 6 prostate cancer on biopsy, the 4Kscore was associated with the prostate cancer being upgraded in the surgical specimen at radical prostatectomy. The 4Kscore test may facilitate the selection of men who can be observed versus those who should undergo immediate treatment.
Prognostic significance of cell cycle regulating protein expressions in gastric carcinoma patients receiving adjuvant chemotherapy.
Authors: Y. Park, S. Jang, S. Lee, H. Park, M. Ryu, B. Ryoo, J. Yook, B. Kim, K. Kim, Y. Kang
Journal: Journal of Clinical Oncology (2010)

4084 Background: Division of a cell is regulated by various cell cycle proteins some of which are known as oncogenes or tumor suppressor genes. Generally, overexpression of G1 phase cyclins and loss of cdk inhibitors are associated with poor prognosis in various carcinomas. Methods: We evaluated expression of Ki-67, cyclin D1, cdk4, p16INK4a, cyclin E and p27Kip1 via immunohistochemical staining in 679 gastric cancer patients who received adjuvant chemotherapy after curative radical gastrectomy. All were eligible patients who had been enrolled for randomized adjuvant chemotherapy clinical trial from 2002 to 2006 in Asan Medical Center. Tissue microarrays were made using two 1.5 mm-tumor cores obtained from paraffin blocks of each case. Results: The expression of cyclin D1 (p = 0.001) and p27Kip1 (p = 0.005) showed positive correlation and p16INK4a (p = 0.033) showed negative correlation with disease free survival in univariate analysis. In multivariate analysis by Cox proportional hazard model, pathologic stage (pTNM, p < 0.001), lymphovascular invasion (p < 0.001), type of gastrectomy (p = 0.011), cyclin D1 (p = 0.009), and p16INK4a expression (p < 0.001) were independent prognostic factors of disease-free survivial. When the cases were grouped according to the cyclin D1 and p16INK4a expression, the cyclin D1 positive and p16INK4anegative group showed the best prognosis and the cyclin D1 negative and p16INK4a positive group showed the worst prognosis. Conclusions: The overexpression of cyclin D1 and loss of p16INK4a is generally considered as poor prognostic factors because cyclin D1 is considered as an oncogene and p16INK4a as a tumor suppressor gene. However, our data suggest that in adjuvant chemotherapy setting, the overexpression of cyclin D1 and loss of p16INK4a are good prognostic factors in gastric carcinoma. No significant financial relationships to disclose.
Relationship of efficacy with <i>KRAS</i> status (wild type versus mutant) in patients with irinotecan-refractory metastatic colorectal cancer (mCRC), treated with irinotecan (q2w) and escalating doses of cetuximab (q1w): The EVEREST experience (preliminary data)
Authors: S. Tejpar, M. Peeters, Y. Humblet, J. B. Vermorken, G. De Hertogh, W. De Roock, J. Nippgen, A. von Heydebreck, C. Stroh, E. Van Cutsem
Journal: Journal of Clinical Oncology (2008)

4001 Background: We previously demonstrated in the EVEREST trial that, in pts with mCRC after failure of irinotecan-based therapy, the efficacy could be improved by escalating the dose of cetuximab in combination with standard-regimen irinotecan (180 mg/m2 q2w) compared with standard-dose cetuximab for pts with grade 0/1 skin reactions. It has been suggested that KRAS mutation status may be a predictor for tumor response to anti-EGFR treatment. The question remains of whether dose escalation is also able to induce response in pts with mutated KRAS. Methods: Pts with grade 0/1 skin reactions after 22 days of treatment with irinotecan and standard-dose cetuximab were randomized to receive standard dose (250 mg/m2) (Arm A) or escalated (up to 500 mg/m2) (Arm B) doses of cetuximab. Archived tissue from 77 of 89 randomized pts was analyzed for KRAS mutation status. Efficacy parameters were determined and compared with the outcome of KRAS mutation analysis. Results: In Arm A, 45 pts were randomized: 19 pts (42%) were KRAS wt, 19 pts (42%) were KRAS mt, and 7 pts (16%) were non-evaluable for the preliminary analysis. In Arm B, 44 pts were randomized and the figures were 28 (64%), 11 (25%), and 5 (11%), respectively. Updated data including PFS and additional correlations of KRAS status with ligands and mRNA predictive signatures will be presented. Conclusions: These data suggest that patients with KRAS wt achieve considerable benefit from irinotecan plus cetuximab treatment. Patients with KRAS mt did not profit from irinotecan plus cetuximab treatment and cetuximab dose escalation did not increase responses in these patients. Response rate Arm A Arm B KRAS wt 4/19 (21.1%) 13/28 (46.4%) KRAS mt 0/19 0/11 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck, Merck Serono Merck Merck Merck, Merck Serono
Exploratory biomarker assessment in the Trastuzumab for Gastric Cancer (ToGA) study.
Authors: F. Lordick, E. Van Cutsem, J. Rüschoff, J. Hill, M. Lehle, A. C. Kiermaier, G. Aprile, Y. Omuro, T. J. Price, Y. Bang
Journal: Journal of Clinical Oncology (2011)

e21029
Effect of treatment-related lymphopenia on survival in newly diagnosed patients with resected adenocarcinoma of the pancreas.
Authors: Ani Sarkis Balmanoukian, Xiaobu Ye, Joseph M. Herman, Dan Laheru, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2012)

270 Background: Severe treatment-related lymphopenia is associated with shorter survival in patients with high grade gliomas. This study was performed to determine if patients with resected pancreatic adenocarcinoma treated with post-operative radiation and chemotherapy develop significant lymphopenia and if this affects overall survival. Methods: Patients selected for this retrospective analysis underwent pancreatic cancer resection between 1997 and 2008, and received post-operative radiation with gemcitabine or 5-FU based chemotherapy at Johns Hopkins Hospital. Serial lymphocyte counts were recorded and survival was analyzed as a function of lymphopenia and known prognostic factors. Results: Fifty-three adults met the eligibility criteria. Their median age was 64, median tumor size was 3 centimeters, 83% underwent a pancreaticoduodenectomy, 47% had positive margins, and 92% had positive nodes. Total lymphocyte counts were normal in 91% of patients prior to receiving radiation and concomitant chemotherapy with 5FU(59%) or gemcitabine (41%). Total lymphocyte counts fell to &lt;500 cells/mm 3 in 45% of patients two months after initiating therapy with a median reduction of 63% from the baseline (p&lt;0.0001). The median survival of patients with lymphocyte counts &lt;500 cells/mm 3 at 2 months was 14 months versus 20 months in patients with more lymphocytes (p=0.0485). Univariate analysis revealed no significant association between pre-treatment patient characteristics and survival. Multivariate analysis revealed a significant association between survival and lymphocyte count (&lt;500 vs ≥ 500 cells/mm 3 ) at 2 months (HR 2.2, p = 0.014). Conclusions: Adjuvant radiation and chemotherapy induced lymphopenia is frequent, severe, and an independent predictor for survival in patients with resected pancreatic adenocarcinoma.
Correlation of biliary stenting with clinical outcome in patients with advanced pancreatic cancer treated with chemotherapy.
Authors: Luca Faloppi, Elena Maccaroni, Riccardo Giampieri, Maristella Bianconi, Alessandro Bittoni, Michela Del Prete, Stefania Antognoli, Mario Scartozzi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2012)

349 Background: The head of the pancreas is a common location for primary pancreatic tumour and therefore obstructive jaundice is a common complication deriving from this location. Although very important in the palliative treatment of this setting of patients, endoscopic procedures are an important source of complications, frequently influencing the prognosis. Aim of our analysis was to assess the clinical outcome of pancreatic cancer patients with biliary stent. Methods: We retrospectively analyzed a population of metastatic or locally advanced pancreatic cancer patients receiving at our Institution a first line chemotherapy between 2002 and 2010. Results: 163 patients were eligible for our analysis, 29 (18%) carried a biliary stent before first line treatment. A statistically significant difference in time to progression (TTP) was found in patients with or without biliary stent (respectively 2.77 months vs 4.27 months p=0,03). Clinical characteristics were homogeneous between the two groups (age, sex, performance status, stage, objective response rate, chemotherapy performed, toxicity profile). Overall survival analysis was worse in patients with biliary stent (5.93 months vs 8.33 months). In the group of patients with biliary stent toxicity was worse in patients receiving a combination chemoterapy (GEMOX). Conclusions: In our population placement of biliary stent seems to have a negative prognostic role in advanced pancreatic cancer patients. Our data also show that in patients with biliary stent the toxicity profile of chemotherapy may influence treatment adherence and clinical outcome. These observations seem to suggest that patients with obstructive jaundice even when successfully treated with plastic or metal stent may still represent a group of patients with a worse clinical outcome, not suitable for an intensive first-line approach such as FOLFIRINOX.