tbuckley/cabot-search huggingface dataset:
Photoselective vaporization of the prostate compared to transurethral resection of the prostate in patients who develop prostatic obstruction following brachytherapy.
Authors: Benjamin Abelson, Chandana A. Reddy, Jay P. Ciezki, Kenneth Angermeier, James Ulchaker, Eric A. Klein, Hadley Wood
Journal: Journal of Clinical Oncology (2013)

187 Background: Patients who undergo brachytherapy are at risk of developing prostatic obstruction, and a subset of these patients requires prostate reduction surgery. These patients pose a challenge to urologists who seek to determine the appropriate form of intervention given the reduced healing capacity of irradiated tissue. Given our observation that certain patients suffer recalcitrant prostatic obstruction following photoselective vaporization of the prostate (PVP), we evaluated outcomes after TURP compared to PVP for patients who experienced bladder outlet obstruction after brachytherapy. Methods: Cleveland Clinic’s prostate cancer database includes 3,600 patients who have undergone prostate brachytherapy since 1996. We cross-referenced these patients with the EMR to identify patients who required prostate reduction surgery following brachytherapy. We reviewed operative notes for these patients to identify the type of intervention completed, and we used the EMR to identify post-PVP/TURP complications requiring intervention. Clinical and demographic characteristics were obtained from the prospective database. Results: Sixty of the 3,600 patients developed urinary retention requiring prostate reduction surgery. The average age of these patients was 69 and the average prostate size was 52 grams. Forty patients underwent TURP and 20 patients were treated with PVP. Of the TURP patients, 19/40 (47.5%) required subsequent TURP, dilation, incision or permanent diversion, including 9 patients (22.5%) who required at least 2 further procedures. Of the PVP-treated patients, 10/20 (50%) required subsequent instrumentation including 4 (20%) who underwent at least 2 procedures. Conclusions: Half of the patients who require prostate reduction surgery for urinary retention following brachytherapy may require further procedures regardless of whether TURP or PVP is performed. Neither procedure confers less morbidity. [Table: see text]
Impact of Recovery of CD4 and CD8 Lymphocyte Subsets on Acute GVHD after Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT).
Authors: Mohamad Mohty, Beatrice Gaugler, Catherine Faucher, Danielle Sainty, Christine Arnoulet, Jean-Albert Gastaut, Patrice Viens, Daniel Olive, Didier Blaise
Journal: Blood (2005)
Prognostic effect of angiotensin-converting-enzyme inhibitors in HCC patients treated with sorafenib.
Authors: Khaled Abouelezz, Ahmed Omar Kaseb, Hesham Mohamed Hassabo, Chris R. Garrett, Jean-Nicolas Vauthey, Donghui Li, Manal Hassan
Journal: Journal of Clinical Oncology (2013)

328 Background: Experimental studies indicated that angiotensin-converting-enzyme inhibitors (ACEs) or angiotensin receptor blockers (ARBs) has a role in reducing malignant changes of the liver and may significantly improve the mortality in patients with other cancers. However it is not known whether ACE and ARB inhibitors may have prognostic impact on HCC survival outcome. We aimed at evaluating the role of ACE inhibitors and ARB blockers on the prognosis of HCC patients who have been treated by Nexavar (sorafenib). Methods: Using resources of our case-control study at MD Anderson, total of 187 (males, 76.5%; females, 23.5%) pathologically confirmed HCC had been treated by sorafenib. The overall mean age (±SD) was 62.5years ± 9.6. The majority of patients were Caucasians (62.6%) who were diagnosed at TNM stage III and IV (79.2%). Total of 89 (47.6%) patients had no evidence of hepatitis C virus (HCV) or hepatitis B virus (HBV). Median survival was calculated using Kaplan Meier product-limit method and survival rates were compared using the log rank test. Cox proportional hazards model was used to estimate the univariate and multivariate Hazard Risk Ratios (HRR) and 95% Confidence Interval (CI). Results: The overall median survival of HCC patients was 19.9 months (95% CI, 16.1-23.6). Intake of ACEs or ARBs inhibitors was reported in 94 patients (50.3%). We observed significant difference in overall median survival (months) between patients who had ACE/ARB inhibitors versus those who did not, median survival (95% CI) were 21.5 (17.1-25.8) and 14.6 (12.4-16.7), respectively, p=0.04. After adjustment for HCC prognostic factors and demographic factors, we observed 30% reduction in HCC mortality among those who received ACEs/ARBs inhibitors, the estimated HR was 0.7 (95% CI, 0.4-1), p=0.05. Conclusions: Our results may indicate that HCC patients under anti-angiogenic therapy (sorafenib) and have been under anti-hypertensive therapy like ACE/ARB may assist in depleting the collagen and may improve host matrix and tumor microenvironment to enhance drug delivery. Future analysis in a larger sample is warranted
A RAND/UCLA appropriateness study of the management of familial gastric cancer.
Authors: Matthew Dixon, Rajini Seevaratnam, Debrah Wirtzfeld, Robin S. McLeod, Lucy K. Helyer, Calvin Law, Carol Jane Swallow, Lawrence Frank Paszat, Jill Tinmouth, Roberta Cardoso, Alyson L. Mahar, Natalie G. Coburn
Journal: Journal of Clinical Oncology (2012)

16 Background: Hereditary diffuse gastric cancer (HDGC) makes up 0.1-0.3% of all gastric cancers. Management of patients with HDGC is inconsistent and there is disagreement regarding management. Methods: A multi-disciplinary expert panel of 16 physicians from 6 countries scored 47 scenarios using the RAND/UCLA Appropriateness Methodology. Appropriateness was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) from 1-3 were considered inappropriate, 4−6 uncertain, and 7−9, appropriate. Agreement was reached when 11 of 16 panelists scored the statement similarly. If a statement was agreed to be appropriate, it was given a necessity score (NS) in the same manner. AS and NS are reported if agreement was met. Results: Gastric cancer (GC) patients with a family history of diffuse gastric cancer (DGC), lobular breast cancer or multiple family members with GC should be referred for genetics assessment and multidisciplinary decision-making (AS 8.0). It is appropriate for patients with DGC to have CDH1 mutation testing in a family with: (1) two or more cases of GC, with at least one case of DGC diagnosed before the age of 50 (AS 8.0); (2) three or more cases of GC diagnosed at any age, one or more of which is DGC (AS 8.0); (3) a patient diagnosed with DGC and lobular breast cancer (AS 8.0); or (4) a patient diagnosed with DGC under the age of 35 (AS 7.0, NS 5.0). A prophylactic total gastrectomy should be offered to CDH1 mutation carriers 20 years or older (AS 7.0). Conclusions: The Gastric Cancer Processes of Care panelists have outlined high risk patients in whom CDH1 mutation status should be determined, and cases in which a prophylactic gastrectomy is appropriate.
Targeting multiple signal pathways simultaneously might provide effective therapeutic strategies in acute myeloid leukemia.
Authors: H. Liu, E. Diaz-Flores, X. Poire, G. Koval, G. Malnassy, M. M. Le Beau, K. Shannon, O. Odenike, W. Stock
Journal: Journal of Clinical Oncology (2011)

6546 Background: MEK/MAPK and PI3K/Akt pathways have been demonstrated to be constitutively activated in the majority of AML patients and associated with poor prognosis, but inhibition of single pathway has only demonstrated modest clinical activity. Methods: The current study evaluated the efficacy of combination of orally available inhibitors to MEK (AZD6244, Astra Zeneca), PI3K/mTOR (NVP-BEZ235, Novartis), Akt (MK 2206, Merck) and Bcl-2 family members (ABT263, Abbott) in human AML cell lines and primary AML patient samples. Results: In MV 4;11 cells (harboring both MLL re-arrangement and FLT3-ITD mutation), AZD6244 or BEZ235 alone moderately decreased viable cells by 30-40%, but combination of these two had dramatic additive effect of cell killing by 70-80%. ABT263 plus AZD6244 or BEZ235 resulted in further additive cell killing effects. While MK2206 alone had little effect, combination of MK2206 with AZD6244 resulted in excellent synergy. Similar effects were observed in HL60 cells with complex karyotype, KG-1 cells with del (5q), and in leukemia cells from 3 AML patients with different cytogenetic abnormalities. Combination therapy induced apoptotic cell death. To evaluate the mechanisms of apoptosis, flow cytometry was used to detect phospho-protein and apoptosis-associated proteins. Interestingly, inhibition of MEK/MAPK with AZD6244 increased pmTOR and Mcl-1 levels, suggesting feedback activation of PI3K/Akt/mTOR pathway, which could be abrogated by BEZ235. AZD6244 also resulted in increased expression of Bim and Bcl-2 in AML cell lines, which could not be abrogated by BEZ235, suggesting that the modulation of these two proteins is independent of the PI3K/Akt/mTOR pathway. This could explain why ABT263 could further sensitize the cell killing by AZD6244 and BEZ235. Conclusions: Our data provide a strong rationale for combinational targeting of PI3K/Akt/mTOR and MEK pathways for the treatment of AML. Furthermore, inhibition of BCl-2 family members by ABT263 may provide additional therapeutic benefit. Based on our pre-clinical findings, a phase I clinical trial to combine AZD6244 with MK2206 through NCI has been proposed to treat patients with refractory or relapsed AML.
A phase 2 study of lenalidomide, rituximab, cyclophosphamide, and dexamethasone (LR‐CD) for untreated low‐grade non‐Hodgkin lymphoma requiring therapy
Authors: Allison Rosenthal, Amylou C. Dueck, Stephen Ansell, Katherine Gano, Christopher Conley, Grzegorz S. Nowakowski, John Camoriano, Jose F. Leis, Joseph R. Mikhael, A. Keith Stewart, David Inwards, David Dingli, Shaji Kumar, Pierre Noel, Morie Gertz, Luis Porrata, Stephen Russell, Joseph Colgan, Rafael Fonseca, Thomas M. Habermann, Prashant Kapoor, Francis Buadi, Nelson Leung, Rodger Tiedemann, Thomas E. Witzig, Craig Reeder
Journal: American Journal of Hematology (2017)

Abstract Patients with indolent non‐Hodgkin lymphoma (NHL) have multiple treatment options yet there is no consensus as to the best initial therapy. Lenalidomide, an immunomodulatory agent, has single agent activity in relapsed lymphoma. This trial was conducted to assess feasibility, efficacy, and safety of adding lenalidomide to rituximab, cyclophosphamide, and dexamethasone (LR‐CD) in untreated indolent NHL patients requiring therapy. This was a single institution phase II trial. Treatment consisted of IV rituximab 375 mg/m 2 day 1; oral lenalidomide 20 mg days 1–21; cyclophosphamide 250 mg/m 2 days 1, 8, and 15; and dexamethasone 40 mg days 1, 8, 15, and 22 of a 28‐day cycle. Treatment continued 2 cycles beyond best response for a maximum of 12 cycles without rituximab maintenance. Thirty‐three patients were treated. Median age was 68 (43–83 years). 39% had stage IV disease. Histologic subtypes included 8 follicular lymphoma (FL), 7 marginal zone lymphoma (MZL) (1 splenic, 2 extranodal, and 4 nodal), 15 Waldenström's macroglobulinemia (WM), 1 lymphoplasmacytic lymphoma, 1 small lymphocytic lymphoma, and 1 low‐grade B‐cell lymphoma with plasmacytic differentiation (unable to be classified better as MZL or LPL). Hematologic toxicity was the most common adverse event. Median time of follow‐up was 23.4 months (range 1.8–50.9). The overall response rate was 87.9%, with 30.3% complete response. The median duration of response was 38.7 months. The median progression free survival was 39.7 months, while median overall survival (OS) has not yet been reached. Lenalidomide can be safely added to a simple regimen of rituximab, oral cyclophosphamide, and dexamethasone and is an effective combination as initial therapy for low‐grade B‐cell NHL.
Identification of novel immunomodulatory tumor biology through comprehensive characterization of a metastases-specific epigenome in patients with metachronous primary and metastatic urothelial carcinoma (UC) tumor pairs.
Authors: Noah M. Hahn, Harvey M Cramer, Sunil S. Badve, Liang Cheng, Yesim Gokmen-Polar, David F Miller, Aaron Buechlein, Douglas B Rusch, Fang Fang, David Frankhouser, Ralf Bundschu, Ganbat Javkhlan-Ochir, Michael O. Koch, Richard Bihrle, Richard Foster, Timothy A. Masterson, Thomas A. Gardner, Pearlly Yan, Kenneth P Nephew, Luigi Marchionni
Journal: Journal of Clinical Oncology (2016)

452 Background: The Cancer Genome Atlas project identified a distinct cluster of hypermethylated muscle-invasive UC tumors in one third of patients. It is unknown if this epigenetic biology persists or changes in UC metastases. The present study aimed to identify uniquely hypermethylated regions in UC metastases compared to their matched primary tumors. Methods: UC patients with paired formalin fixed paraffin embedded tissue samples ( &gt; 75% tumor) from primary and metachronous metastatic tumors were identified. DNA methylation was analyzed on the Illumina HiSeq platform by double-enzyme reduced representation bisulfite sequencing (dRRBS). Results were analyzed by BS-seq within BSmooth open source software. Alignment and methylation estimation was done using Bismark open source software. CpG regions with coverage &lt; 2 in more than 66% of samples were removed to reduce false positive results. Differentially methylated regions (DMRs) in metastases compared to primary tumors were determined by paired t-test. Gene set enrichment analysis (GSEA) of the top 5% DMRs was performed utilizing multiple gene set collections including c7IMMUNO. A false discovery rate of &lt; 10% defined significant DMRs. Results: 15 UC primary/metachronous metastases pairs were analyzed. After filtering for low coverage, 1,781,762 loci remained for analysis. After merging loci within 2500 bp of each other, the top 5% DMRs resulted in 18,452 DMRs. GSEA including the c7IMMUNO gene set identified multiple previously undescribed hypermethylated genes modulating immune function through TGF-beta and Treg signaling including: TGFBR2, TGFBR3, SMAD1, SMAD3, SMAD4, BACH1, BACH2, and VDR all q &lt; 0.05. Conclusions: We identified numerous genes with immunomodulatory functions significantly hypermethylated in UC metastases compared to their matched primary tumors. Our findings provide rationale to examine epigenetic approaches as a means to improve clinical outcomes of UC patients treated with immunotherapy. Our small sample size limits definitive conclusions and warrants validation in independent data sets.
Screening for mutations in Colombian metastatic non-small cell lung cancer (NSCLC) patients (ONCOLGroup).
Authors: A. F. Cardona, P. L. Ramos, R. Duarte, H. Carranza, C. J. Castro, M. Lema, C. A. Vargas, A. Jimenez, H. A. Becerra, R. Rosell
Journal: Journal of Clinical Oncology (2011)

7577 Background: Driver mutations occur in genes that encode signalling proteins critical for cellular proliferation and survival. In lung cancer, these mutations include EGFR, KRAS, BRAF and EML4/ALK. Methods: We evaluated the feasibility of screening 228 NSCLC patients in Colombia by analyzing tumor tissue by DNA sequencing. Results: The study included 152 females (67%) and 76 males (33%) with a mean age of 59 (SD ± 13); 63% of the patients had adenocarcinoma, 6% presented non-specific tumors, 1.8% had large cell carcinomas, 2.6% had squamous cell carcinomas. Histological subtype was non-specific in 12.3%. According to tobacco consumption (n=173), 60%, 20% and 3% were non-smokers, ex-smokers or active smokers respectively. 57 patients had activating mutations (25%) in the EGFR, 40 with E19 deletion (70% of mutated subjects) and 17 with the in-frame L858R mutation (30%). Almost all with the E19 deletion were non-smokers (86%), as well as those affected by the E21 mutation (75%). 11% of tumors were positive for K-ras mutations (n=114), one patient (3.8%) was positive for the ALK/ELM4 fusion gene (n=26). BRAF (V600E) mutations were not detected (n=60). Conclusions: The frequency of mutations in EGFR in NSCLC patients from Colombia was greater than that reported in other western countries; the distribution favoured the presence of the E19 deletion and the proportion of ALK/ELM4 is in agreement with previous data. To our knowledge, this study represents the first comprehensive analysis of major oncogenic mutations found in a large cohort of lung cancers from Latin America.
Metastatic colorectal cancer and management in public versus private hospitals: Similarities and differences.
Authors: Kathryn M Field, Jeremy David Shapiro, Joseph J McKendrick, Hui-Li Wong, Jayesh Desai, Lara Rachel Lipton, Suzanne Kosmider, Louise M. Nott, Gregory Stefanou, Phillip Parente, Allan Solomon Zimet, Lionel Lim, Ross Jennens, Desmond Yip, Matthew E. Burge, Peter Gibbs
Journal: Journal of Clinical Oncology (2013)

497 Background: Potential differences between public and private cancer care in Australia include the degree of subspecialisation, multidisciplinary clinic review, access to clinical trials and continuity of care, all of which could impact treatment and outcomes. Here we compared demographics, tumour details, treatment and survival outcomes for patients (pts) with newly diagnosed metastatic colorectal cancer (mCRC) treated in the public versus private setting. Methods: This research was conducted using the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) mCRC clinical research database. Data collection began in June 2009 and is ongoing at 15 Australian centres. Here, data from four public and eight private hospitals are presented. Results: Of 671 pts, 253 (38%) were treated at public hospitals and 418 (62%) at private centres. For public versus private pts there was no significant difference in median age or percentage with good performance status. More private pts received first-line chemotherapy (89% vs 80%, p=0.002), but there were no significant difference in the use of bevacizumab (50% versus 43%, p=0.10). Similar proportions received combination therapy (72% private vs 68% public) but the use of single agent oral capecitabine was higher for private patients (9% vs 4%, p=0.03). More public pts were enrolled in a first-line clinical trial (17.3% vs 1.2%, p&lt;0.0001). Preliminary analysis suggests improved overall survival for private pts (26 months versus 17 months, p&lt;0.001). Conclusions: While public and private pts in this cohort were similar in age and performance status, significantly more private pts were given chemotherapy, but similar proportions were given bevacizumab and far less were enrolled on first-line clinical trials. This may relate to availability of first-line trials during this period. The superior survival outcomes achieved in private practice must be further explored, and might reflect a more intense approach to treatment, yet-to-be identified differences in patient characteristics, or differences in quality of care.
Autologous stem cell transplantation (ASCT) for locally advanced breast cancer (LABC) and inflammatory breast cancer (IBC): University of Iowa (UI) experience 1992–2007
Authors: R. Gingrich, A. Thomas, B. J. Smith, M. Silverman
Journal: Journal of Clinical Oncology (2008)

11511 Background: At UI a unique, highly intensive myeloablative regimen of cisplatin, etoposide, thiotepa and cyclophosphamide (PET-CY) was utilized for patients (pts) with high risk breast cancer. Methods: Records of 97 consecutive, clinical trial pts with LABC and IBC were reviewed. Pts were rigorously screened to exclude systemic disease. Univariate analyses were performed for overall survival (OS) and disease-free survival (DFS). Treatment-related mortality (TRM), frequencies of life-threatening toxicities and second malignancies were also reviewed. Results: Median follow-up among 44 current survivors was 9.6 years (3.5 - 15.2). For all pts the median tumor size at surgery was 3.5 cm and the median number of involved lymph nodes was 11. Neoadjuvant chemotherapy had been given in 70% of pts with IBC and 13% pts with LABC. OS and DFS are reported in the table. Tumor sizes, E-E grade, surgery type, date from diagnosis to transplant, and neoadjuvant treatment did not influence OS or DFS. In patients with LABC, ER positive patients had statistically significant improved OS (HR for death 0.45, p = 0.03). TRM at 100 days was 11%. 16% of patients had life threatening complications. Stomatitis was frequent and severe: 6 patients required intubation for this. Second cancers developed in 8 patients. Conclusions: This analysis provides long-term follow-up on patients treated with PET-CY myeloablative regimen with ASCT for high risk breast cancer. Treatment related morbidity and mortality were high. Fewer second malignancies were seen than have been reported in other series. These data provide an estimate of long-term outcome for patients with high-risk breast cancer, screened for participation in a clinical trial to exclude systemic disease and treated with a highly intensive, multi-agent chemo-ablative regimen. Survival rate of overall survival and disease-free survival Survival Rate (95% CI) Inflammatory Breast cancer Locally Advanced Breast Cancer Overall 100 days 0.87 (0.69, 0.95) 0.89 (0.79, 0.95) Survival 5 years 0.54 (0.36, 0.70) 0.65 (0.52, 0.75) 10 years 0.35 (0.17, 0.55) 0.47 (0.33, 0.59) Disease-free survival 100 days 1 0.97 (0.87, 0.99) 5 years 0.59 (0.39, 0.75) 0.67 (0.54, 0.78) 10 years 0.53 (0.31, 0.71) 0.49 (0.35, 0.67) No significant financial relationships to disclose.
Clinical significance of metastatic-tumor HER2 status in patients with HER2-positive primary breast cancer.
Authors: N. Niikura, J. Liu, N. Hayashi, E. A. Mittendorf, Y. Gong, S. L. Palla, Y. Tokuda, A. M. Gonzalez-Angulo, G. N. Hortobagyi, N. T. Ueno
Journal: Journal of Clinical Oncology (2011)

545 Background: Studies have suggested that trastuzumab may convert HER2-positive (HER+) primary breast tumors to HER2-negative (HER2–). Whether this conversion happens between primary and metastatic lesions is unknown. We tested the hypothesis that trastuzumab increases the number of patients with HER2+ primary tumors and HER2– metastases (HER2 discordance). We assessed the same effect of chemotherapy. We also compared overall survival (OS) durations of patients with HER2 discordance and patients with HER2 concordance (ie, HER2+ primary and metastatic tumors). Methods: We retrospectively identified 182 patients who had been diagnosed with HER2+ (IHC 3+ and/or FISH+) primary breast cancer in 1997–2008 at MD Anderson Cancer Center and had known HER2 status of the metastasis. Median follow-up was 18 (1-90) months. OS rates were determined using the log-rank test and Cox proportional regression models. Results: Of 182 patients with HER2+ primary tumors, 43 (24%) had HER2– metastases (discordance). Of 76 patients who received trastuzumab before their metastasis biopsies, 15 (20%) had HER2 discordance. Similarly, of 106 patients who did not receive trastuzumab before their metastasis biopsies, 28 (26%) had discordance. There was no significant difference in discordance rates based on trastuzumab (P = .296). However, discordance rates differed significantly based on chemotherapy (P = .022); 39 (27%) of 142 patients who received chemotherapy (with or without trastuzumab) before their metastasis biopsies had discordance, compared with 4 (10%) of 40 patients who did not receive chemotherapy. Patients with HER2 discordance had shorter OS than patients with HER2 concordance (hazard ratio = .43; P= .003). A survival difference remained among the 67 patients who received trastuzumab before their metastasis biopsies (hazard ratio = .56; P = .083). Conclusions: One-fourth of primary HER2+ breast cancers converted to HER2–. Our hypothesis was rejected; trastuzumab did not affect discordance rate, although chemotherapy did. Patients with HER2 discordance had poorer prognoses than those with concordance. A prospective study is warranted to determine whether HER2 discordance affects prognosis and treatment.