tbuckley/cabot-search huggingface dataset:
Tumor thrombus transection in renal cell carcinoma.
Authors: Joseph C. Klink, Karin E. Westesson, Tianming Gao, Andrew J. Stephenson, Venkatesh Krishnamurthi
Journal: Journal of Clinical Oncology (2013)

409 Background: Inferior vena cava (IVC) tumor thrombectomy with radical nephrectomy (RN) for renal cell carcinoma (RCC) is difficult when a large renal mass is present, but completing the RN by transecting the renal vein with tumor thrombus inside can facilitate dissection of the IVC for thrombectomy. We compared the outcomes of patients in whom the thrombus was purposely transected to those in whom the IVC thrombus was removed en bloc with the kidney. Methods: At our institution between 2000-2011, 152 patients with RCC and level II (N =53), III (N =52) or IV (N =47) IVC thrombus underwent RN and IVC thrombectomy. In 92 patients the kidney was removed prior to initiating the IVC thrombectomy. In 60 patients, the tumor thrombus and kidney were removed en bloc. Clinical information was obtained from an institutional database. Since thrombus level greatly affects surgical technique and complications, outcomes were analyzed within each level. Results: Thrombus level and clinical stage were higher in the transected group, but other baseline characteristics did not differ significantly. The primary endpoint, the overall rate of complications including intra-op and post-op events, was not statistically significantly different (all p &gt;0.2) between the en bloc and transected groups for level 2 (8/37 vs. 6/16), level 3 (7/17 vs. 15/35), and level 4 (2/6 vs. 25/41). Operative times were similar within level 2 (300 vs. 300 minutes, p=0.2), level 3 (312 vs. 360, p=0.1), and level 4 (325 vs. 402, p=0.7). Units of blood products transfused were also similar within level 2 (3 vs 5, p=0.3), level 3 (5 vs. 9, p=0.06), and level 4 (6 vs. 14, p=0.4). Due to the low event numbers within each subgroup, multivariable analysis could not be reliably run on these outcomes. Three patients, all in the transected group, experienced intraoperative tumor thrombus embolization to the pulmonary artery requiring surgical embolectomy, but all 3 survived to discharge without any serious sequelae. Conclusions: Complications, operative time, and transfusion rates were similar between the en bloc and transected techniques when stratified by tumor thrombus level. Because of the rarity of this disease, statistical power of these comparisons is low, but our study suggests no evidence of advantage to either technique.
Using Bayesian proof-of-concept criteria to design randomized phase II oncology trials stratified by biomarker status.
Authors: K. V. Appanna, E. P. H. Zuber, V. Jehl, Y. Zhang, Y. Wang, A. racine-Poon, B. Neuenschwander
Journal: Journal of Clinical Oncology (2011)

e21150 Background: In the early stage development of a targeted therapy, assumed to be more effective in a specific subpopulation, it is very challenging to decide whether clinical trials should be conducted in all patients or only in the specific subpopulation. We propose to use randomized Phase II study results to help make the decision about which population to use in a subsequent Phase III study. Traditional frequentist designs often use Type I/II error rates only to determine sample sizes and make decisions based on p-values. However, critical values needed for statistical significance are often implicit and a significant p-value does not necessarily imply a clinically meaningful effect size. Therefore, we propose some Bayesian proof-of-concept (PoC) criteria with clearly defined effect size criteria. Methods: Bayesian PoC criteria are proposed for all patients, biomarker positive patients, and biomarker negative patients, respectively. These criteria require 1) a reasonably high probability that treatment is better than control and 2) the estimated hazard ratio is in favor of the treatment and reaches a clinically meaningful size. We then establish a decision rule based on the PoC criteria for the three study populations. Frequentist probabilities of making the right decision for various scenarios are investigated. Additionally, when the prevalence rate for positive biomarker is low, it may be desirable to enrich the Phase II study in biomarker positive patients, which requires adjusted estimates for the hazard ratios in the original population. Results: Simulations show that the proposed design has good frequentist operating characteristics. The proposed design has been applied in a new randomized Phase II trial in breast cancer. Conclusions: A new Phase II oncology design using Bayesian PoC criteria is proposed. This design is easy to interpret, has good operating characteristics, and can avoid some potential shortcomings in traditional designs.
Temporal trends in the management of localized prostate cancer: From 2004 to 2011.
Authors: Phillip John Gray, Chun Chieh Lin, Ahmedin Jemal, Jason Alexander Efstathiou
Journal: Journal of Clinical Oncology (2015)

42 Background: The management of localized prostate cancer (PC) is evolving. We sought to analyze recent management trends using a large national database. Methods: Data on patients presenting with a new diagnosis of PC between 2004 and 2011 were extracted from the National Cancer Data Base. Patients with nodal or distant metastases were excluded. Patients were categorized as low risk (LR), intermediate risk (IR) or high risk (HR) according to the National Comprehensive Cancer Network’s (NCCN) guidelines. Multivariate logistic regression was performed to identify factors associated with the receipt of surgery or radiotherapy. Results: 823,977 patients met the study criteria; 38.5% were LR, 42.7% IR and 18.9% HR. Between 2004 and 2011, for LR patients, rates of observation after diagnosis increased from 12.4% to 18.5% and receipt of radical prostatectomy (RP) increased from 40.3% to 54.4% (p for trend both &lt;.001). In contrast, receipt of brachytherapy decreased from 24.4% to 11.4% and receipt of external beam radiation therapy (EBRT) decreased from 18.2% to 13.4% (p both &lt;.001). For IR patients rates of observation increased from 6.1% to 7.3% and RP from 48.1% to 58.5% (p both &lt;.001) while receipt of brachytherapy decreased from 12.1% to 6.4% (p &lt;.001) and receipt of EBRT plus androgen deprivation therapy (ADT) fell from 14.7% to 8.7%. For HR patients, receipt of RP increased from 30.6% to 41.3% (p &lt; .001) while receipt of EBRT plus ADT decreased from 30.4% to 28.0% (p &lt;.001). On multivariate analysis factors predicting for a lower odds of receiving RP vs. radiotherapy (p all &lt;.001) included black race (OR 0.52 vs. white), lack of insurance or insurance through Medicaid (OR 0.66 and 0.50 vs. private insurance) and residing in low income level areas (OR 0.85 for areas in the lowest national quartile vs. the highest). Conclusions: Utilization of radical prostatectomy for patients with localized PC increased significantly across risk groups from 2004 to 2011 while utilization of radiotherapy decreased. Rates of observation have increased in LR disease but remain low overall. Markers of poor socioeconomic status appear associated with receipt of radiotherapy. Further work is needed to elucidate the causes and appropriateness of these trends.
Phase I dose-escalated image-guided adaptive bladder radiotherapy study: Results of first dose cohort (68Gy).
Authors: Robert Huddart, Fiona McDonald, Shaista Hafeez, Karole Warren-Oseni, Helen Taylor, Alan Thompson, Vincent Khoo, Victoria Harris, Helen McNair, Kabir Mohammed, Karen Thomas, Kelly Jones, David Paul Dearnaley, Alan Horwich
Journal: Journal of Clinical Oncology (2014)

291 Background: Prospective study assessing the safety of dose escalation in the treatment of localised muscle-invasive bladder cancer using image-guided adaptive radiotherapy (RT) with a reduced high-dose tumour volume. Methods: Radical RT was planned and delivered in 3 phases. Phase I was delivered to the empty whole bladder (10Gy 5#). Bladder variation assessed on phase I daily imaging was used to determine the adaptive approach for phase III (composite volume or plan of the day). Phase II was delivered to a tumour boost volume on a partially filled bladder (18Gy 9# if normal tissue dose-constraints were met, or to 14Gy 7# if they were not). The adaptive phase III (40Gy 20#) was delivered to the empty whole bladder. The primary endpoint was late RTOG toxicity. Results: Of the twenty-six patients recruited to 68Gy, 20 patients met the normal tissue constraints for dose escalation. For the phase III adaptive technique, 14 patients were treated with a composite volume approach and 12 with a plan of the day. At median follow-up of 24 months, 13 (65%) dose escalated patients remain alive and disease free. Within this dose cohort there has been 1 muscle invasive local recurrence, 1 superficial recurrence and 1 patient has developed metastases. 5 patients in the dose-escalated group have died; 3 from cardiac events, 1 from hospital acquired pneumonia and 1 from metastatic bladder cancer. 1 patient in the dose-escalated group has experienced grade 3 late toxicity (cystitis) occurring 24.6 months after the end of radiotherapy. Conclusions: Image-guided adaptive RT techniques with reduced high-dose volume allow tumour dose-escalation. Toxicity data to date suggest tolerability of 68Gy. Local disease control rates are promising. Trial recruitment continues at 70Gy using intensity modulated radiotherapy technique to deliver a simultaneous integrated boost. Clinical trial information: 7653.
Gene expression profiling in formalin-fixed, paraffin-embedded (FFPE) benign and cancerous prostate tissues using universal bead arrays
Authors: J. M. Yeakley, M. Bibikova, E. Chudin, E. Wickham, J.-B. Fan, T. Downs, J. Modder, M. Kostelec, A. Arsanjani, J. Wang-Rodriguez
Journal: Journal of Clinical Oncology (2005)

9526 Background: Archival tissues from patients with known clinical history have become an invaluable resource for gene expression analysis for tumor classification and clinical outcome prediction. These samples may be studied using qPCR, but RNA extracted from FFPE tissues is often significantly degraded, making them difficult to use in microarray analyses. Methods: We have developed the DASL assay, a flexible, sensitive and reproducible expression profiling method for parallel analysis of hundreds of genes in FFPE samples using universal bead arrays. The method can tolerate partial RNA degradation because it does not depend on an intact poly-A tail for cDNA synthesis. Tissue- and cancer-specific expression profiles have been obtained with as little as 50 ng total RNA derived from FFPE tissues that had been stored up to 11 years (Bibikova, et al., Am. J. Pathol. 165:1790–1807, 2004). Results: We performed a profiling study of 174 benign or cancerous prostate FFPE tissues retrieved from the VA San Diego Healthcare System. A total of 512 prostate cancer-related genes selected from the literature were monitored at 3 probes per gene. Despite RNA degradation, highly reproducible expression profiles were obtained for these samples (average r2 = 0.98). Expression data were used to identify tumor- and stroma-specific genes, which were then included in a sample classification scheme. Resulting gene panels correlated with clinical parameters such as tumor type, tumor grade, therapeutic response, and patient survival. In additional studies using laser capture microdissection of FFPE tissues, increased expression of tumor- and stroma-specific genes were measured in the correct cell types, confirming the results based on heterogeneous tissues. Conclusions: Putative prostate cancer biomarkers were identified using the DASL expression assay and RNAs derived from FFPE patient samples. In combination with the high-throughput capability of the bead array-based platform, the DASL assay may be used to monitor hundreds of genes in hundreds of samples at once. These data suggest that FFPE tissue archives, with known patient outcomes, can now be accessed for microarray expression analysis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Illumina Illumina
A phase II trial of pre-operative paclitaxel and paraplatin in women with newly diagnosed operable breast cancer
Authors: L. Nabell, A. Forero, M. Urist, H. Krontiras, J. Dubay, C. Falkson
Journal: Journal of Clinical Oncology (2005)

794 Background: Combination therapy with paclitaxel and paraplatin are known to have produced significant response rates in the setting of metastatic breast cancer when used as a solo regimen or when combined with Herceptin. The efficacy of this combination is not known in the setting of neoadjuvant treatment of breast cancer. We have initiated an open label Phase II study of neoadjuvant combination therapy with paclitaxel and paraplatin in patients with newly diagnosed stage II carcinoma of the breast. Objectives of the trial include the clinical response and pathologic complete response (pCR) to a maximum of 4 cycles of neoadjuvant therapy, and assessment of tolerability of this regimen in a chemotherapy naïve population. Methods: Patients with newly diagnosed biopsy proven breast cancer were recruited from the UAB Interdisciplinary Breast. Patients were assessed for the type of surgery that would be performed at the time of diagnosis, with axillary nodal status determined clinically or by sentinel lymph node (SLN) biopsy. Patients were asked to undergo an extra tumor biopsy, which was snap frozen to be used for correlative studies including markers of response. Treatment consisted of concomitant paclitaxel (200 mg/m2) and paraplatin (AUC = 6) every 21 days for a total of 4 cycles. A target population of 30 patients has been reached for this study. Results: Since 10/02 30 patients have enrolled on the study, of which 26 have completed therapy. Approximately half of the patients have agreed to an additional biopsy. In patients who completed the treatment phase and have undergone surgery (n = 22) the pCR is 18%. Toxicities have included 1 case of Gr 2 neuropathy and 1 case of Taxol hypersensitivity. Conclusion: The results of this study thus far suggest a response rate that appears to be similar or slightly higher then that achieved with a comparable number of adriamycin based treatments. Toxicity has been minimal and largely self-limited to myalgias and transient myelosuppression. No correlation was seen with ER/PR status. The study is still ongoing, and an update of this data will be provided. Results: Conclusions: No significant financial relationships to disclose.
Preoperative C-reactive protein combined with SSIGN score as an independent predictor of cancer-specific survival in patients with clear cell renal cell carcinoma.
Authors: Lindsey Allison Herrel, Caroline Gar-Ling Tai, Ruth Westby, Ken Ogan, Daniel Canter, John Pattaras, Peter Nieh, Viraj A. Master
Journal: Journal of Clinical Oncology (2013)

451 Background: Renal cell carcinoma (RCC) demonstrates heterogeneous behavior. Approximately 30% to 40% of patients with clinically localized RCC will later metastasize. Current tools are imperfect for predicting who will have distant spread of disease. C-reactive protein (CRP) levels and the Mayo Clinic SSIGN scores are widely use to predict outcomes of clear cell RCC. We investigated the predictive value of the combined use of pre-operative CRP and SSIGN score for cancer specific survival. Methods: Patients undergoing nephrectomy for clinically localized RCC from 2005 to 2010 were studied. Inclusion criteria required clear cell histology, no nodal or metastatic disease at the time of surgery, two years follow-up time, and a recorded preoperative CRP level. SSIGN score was based on postoperative data and was categorized into scores 0-2, 3-5, and ≥ 6. A cut-point of 20 mg/l was used to classify elevated preoperative CRP. Univariate analysis identified variables associated with cancer specific survival (CSS). Variables significant in univariate analysis at p &lt; 0.05 were entered into a multivariate Cox regression model using forward stepwise regression to identify significant predictors of CSS. Results: Study criteria identified 284 patients. Of these patients, 62% were men and 13% had preoperative CRP values ≥ 20 mg/L. No patients had T4 disease, while 22% had T3, 7% had T2, and 70% had T1 disease. SSIGN scores of 0-2, 3-5, and ≥ 6 were assigned to 57%, 30%, and 13% of patients, respectively. On univariate analysis CRP ≥ 20 mg/L was a statistically significant predictor of CSS (p &lt; 0.0004, HR 7.07, CI 95% 2.42, 20.68). Multivariate Cox Regression found preoperative CRP (p = 0.033, HR 3.65, CI 95% 1.11, 11.97) to be an independent predictor of CSS despite controlling for age at surgery (p &lt; 0.05) and SSIGN score (p &lt; 0.05), which were also independent predictors of CSS. Conclusions: In patients with clear cell RCC, pre-operative CRP levels in combination with SSIGN score provides additional information for predicting CSS.
The Prognostic Value of TP53 Mutations in Chronic Lymphocytic Leukemia (CLL) Is Independent of del17p13: Implications for Overall Survival and Chemorefractoriness
Authors: Davide Rossi, Michaela Cerri, Clara Deambrogi, Elisa Sozzi, Stefania Cresta, Silvia Rasi, Lorenzo De Paoli, Daniela Capello, Valter Gattei, Francesco Forconi, Francesco Lauria, Gianluca Gaidano
Journal: Blood (2008)
Individualised monitoring of patients with metastatic melanoma using plasma DNA
Authors: Jonathan Wan, Suzanne Murphy, Davina Gale, James Morris, Florent C Mouliere, Francesco Marass, Katrin Heider, Dineika Chandrananda, Graham Bignell, Christine Parkinson, Amer Durrani, Ultan McDermott, Charles Massie, Pippa Corrie, Nitzan Rosenfeld
Journal: The Lancet (2017)
Prognosis of gastric cancer (GC) patients with positive peritoneal cytology.
Authors: Hironori Shiozaki, Elena Elimova, Rebecca Slack, Hsiang-Chun Chen, Gregg A Staerkel, Nour Sneige, Venkatram Planjery, Nikolaos Charalampakis, Roopma Wadhwa, Kazuki Sudo, Aurelio Matamoros, Jeffrey H. Lee, Brian Weston, Manoop S. Bhutani, Mariela A. Blum, Jeannelyn Estrella, Prajnan Das, Paul F. Mansfield, Brian D. Badgwell, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2015)

41 Background: Laparoscopic staging of patients with GC can disclose peritoneal metastases. Although this finding is associated with a poor prognosis, some patients achieve a long-term survival. In an attempt to provide explanation we compared the overall survival (OS) of patients with GC peritoneal metastases from two settings: cytology positive only (Cy+) and grossly positive (Gross+). Methods: 146 GC patients with peritoneal metastases were identified between 2000 and 2014. Cox-model regression was used for overall survival (OS) analyses. Results: Patient/treatment characteristics were as follows: males (66%), good ECOG scores (0-1; 89%), metastases confirmed by a diagnostic laparoscopy (84%), poorly differentiated histology(92%), received chemotherapy (89%), received chemoradiation (22%), and received surgery (10%). The median follow-up time for all patients was 12.9 months and median OS was 15 months. Patients with Gross+ were at higher risk of death compared to Cy+ patients (50% vs. 83%1-year OS, respectively). Only diagnostic laparoscopy and metastasis type (Gross+ vs. Cy+) were significant in both univariate and multivariate OS models. With both factors in the same model, patients with Gross+ were more than twice as likely to die when compared to those with Cy+ (HR=2.23; p=0.001) while patients having a diagnostic laparoscopy were half as likely to die (HR=0.52; p=0.01). Conclusions: The one-year OS of patients with Cy+ peritoneal metastases is significantly longer than those with Gross+ findings. As such, novel strategies for Cy+ patients may further prolong their survival. From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. (Supported in part by UTMDACC, and CA 138671 and CA172741 from the NCI).
Coping with moderate to severe chronic graft-versus-host disease (cGVHD) among hematopoietic stem cell transplant (HCT) survivors: A qualitative analysis.
Authors: Sarah Fishman, Areej El-Jawahri, Lara Traeger, Harry VanDusen, Yi-Bin Albert Chen, Jennifer S. Temel, Jessica Driscoll
Journal: Journal of Clinical Oncology (2016)

257 Background: HCT survivors with moderate to severe cGVHD experience substantial symptoms, which negatively impact their quality of life. However, data are lacking on how patients cope with their illness. We aimed to achieve a deeper understanding of patients’ illness perception and how they cope with their cGVHD. Methods: We conducted qualitative interviews with 14 HCT survivors with moderate to severe cGVHD as defined by NIH Consensus Criteria. We used a semi-structured interview guide to elicit patients’ illness perception and coping strategies. Two raters coded interviews independently. We used content analysis to identify themes. Results: Patients highlighted two key themes in their efforts to cope with what they perceived as a “full time job” dealing with their cGVHD: personal transformation and empowerment. With respect to transformation, patients expressed the importance of (1) changing the goal of care from recovery to coping with a chronic condition, and (2) seeking new sources of support and connectedness specifically from other patients and caregivers affected by cGVHD. With respect to empowerment, patients sought more information and understanding about cGVHD in order to gain more control over their symptoms and illness experiences. Patients also noted the importance of knowledge and control in coping with their disease. By seeking knowledge and a greater understanding of their disease, patients explained that they felt that they were gaining control and feeling more empowered. Through the lens of change, it is clear that all patients sought an evolution in their care perspective by increasing care motivation, creating active support webs, and seeking further involvement in their own care. Conclusions: The diagnosis and course of cGVHD is psychologically transformative for patients. Although patients demonstrated an understanding of how they cope with the psychological and physical burden, they also expressed a wish for more education, support and a method of connecting with other HCT survivors. Future interventions should focus on enhancing patients’ coping strategies, knowledge of their illness and connections with other HCT survivors.