tbuckley/cabot-search huggingface dataset:
Taste and smell abnormalities (TSA) in patients with newly diagnosed malignant gliomas (MG) treated with combined modality therapy (CMT).
Authors: G. J. Lesser, L. D. Case, S. Mirlohi, M. Harmon, M. Chan, S. Duncan, A. Dietrich
Journal: Journal of Clinical Oncology (2011)

e19646 Background: TSA are common complications of cancer therapy which may lead to impaired nutrition and diminished quality of life. We performed a pilot clinical trial to characterize the frequency, intensity and time course of TSA in patients with MG receiving standard radiation (RT) with concurrent and adjuvant temozolomide (TEM). We also utilized serial salivary analyses to explore the relationship between TSA and lipid peroxidation in the oral cavity, a putative mechanism of metallic taste in other model systems. Methods: Eligible patients completed a validated TSA questionnaire prior to CMT and then again at 3, 6 (completion of RT), 10, 18 and 30 weeks. This tool provided a total chemosensory complaint score (CSCS) with a scale of 0 (normal) to 16 (maximally impaired). Paired samples of saliva were collected at each timepoint following an oral rinse with both a weak ferrous and a control solution. The salivary concentration of lipid peroxidation byproducts was determined using standard colorimetric techniques (TBAR analysis). Results: 17/22 enrolled patients had at least baseline and 6 week CSCS data and were eligible for analysis: Sex - 10M/7F, median age - 58 (range 19-78), Path - 10 GBM, 1 AA, 1 AO, 3 LGO, 1 LGA, 1 LGOA. All analyzed patients completed RT (54-60 Gy), 15/17 completed concurrent TEM, 8/17 completed 6 adjuvant cycles of TEM, and 2 also received investigational agents. Analysis of serial CSCS segregated patients into 3 distinct groups. Group 1 (5 pts)- no TSA at baseline or during CMT; Group 2 (8 pts) – no TSA at baseline but developed TSA during CMT; Group 3 (4 pts)– TSA present at baseline and persisted during CMT. TSA developed within 6 weeks in 7/8 pts in Group 2 and TSA persisted in all Group 2 and 3 pts tested thus far at 18 weeks (5/12). When compared with Group 1, Group 2 pts were more likely to have GBM (7/8 vs 1/5, p=.032) and to have temporal lobe lesions (4/8 vs 0/5, p=.105). No clear correlation was seen between CSCS and the concentration of salivary lipid peroxidation byproducts. Conclusions: TSA can occur in newly diagnosed patients with MG or develop during CMT. These changes develop rapidly during treatment and typically persist for months following the completion of radiation.
Self-reported symptom burden among patients receiving bevacizumab versus cetuximab containing regimens as second-line treatment of metastatic colorectal cancer.
Authors: M. S. Walker, E. Yu, J. Kerr, Y. M. Yim, E. J. Stepanski, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2011)

e16598 Background: Bevacizumab (B) and cetuximab (C) are both approved for use in treatment of metastatic colorectal cancer (mCRC) in the second line. We examined self-reported symptom burden as collected by the 86-item Patient Care Monitor (PCM) survey during second line treatment of mCRC delivered in the community setting. Methods: This was a retrospective study of existing data drawn from the ACORN Data Warehouse. Eligible patients had a diagnosis of mCRC, were age ≥18, and had received second line treatment with a regimen that included B, C, or chemotherapy only (O). Patients had completed ≥ 1 PCM surveys, collected as a routine part of clinical care. Primary endpoints were self-reported rash, dry skin, itching, nail changes, nausea, vomiting, burning in hands/feet, and diarrhea. Linear mixed models examined change in PCM scores during second line, across B, C and O, with B as reference for group comparisons. Models controlled for relevant covariates and for baseline PCM scores. Results: A total of 186 patients were enrolled (B: n=107, C: n=38, O: n=41). Patients were 51% female, 67% Caucasian, with mean age of 61.9 (SD=12.5). Groups did not differ on demographic or clinical characteristics. The most common second line regimens were FOLFIRI ± B or C (26%) and FOLFOX ± B or C (15%). All but 6 patients (2 B and 4 C) patients received chemotherapy. Results showed baseline scores to be strongly predictive of second line symptoms across all PCM items (all p < .0001 except for Rash, p = .0013). Controlling for baseline, the following mixed model results were observed for self-reported symptoms during second line (Table). Conclusions: Patients receiving second line treatment of mCRC with B self-report fewer treatment-related symptoms compared to patients treated with C. Mixed model results Symptom Time trends Group differences Diarrhea Improving (p < .0001) No differences Rash Stable C > B = O (p < .0001) Itching Stable C > B = O (p = .0002) Dry skin Worsening for C (p = .0037) C > B = O (p = .0008) Nail changes Worsening for C (p = .018) No differences
Molecular classification of sunitinib response in metastatic renal cell carcinoma (mRCC) patients by gene expression profiling.
Authors: V. J. Thodima, A. M. Molina, X. Jia, J. Zhang, M. E. Georges, S. Patil, V. E. Reuter, R. J. Motzer, R. S. Chaganti
Journal: Journal of Clinical Oncology (2011)

4556 Background: Sunitinib produces objective response rate of nearly 50% with improved progression-free survival compared to interferon in a randomized phase III trial (JCO 2009;27:22). Identification of molecular markers could improve outcome prediction and improve our understanding of mechanisms of resistance. Methods: Expression profiling was performed on 43 clear cell RCC fresh frozen tumors from pts treated with sunitinib. Median progression-free survival (PFS) was 10 mos (95% CI 6.6-11.9); median OS was 23 mos (95% CI 14-49). Eleven pts had complete and partial response (CR+PR) and 32 pts had progressive and stable disease (SD+PD). RNA isolated from tumor samples was amplified and profiled using Affymetrix microarray. The prognosis predictor models were built using a Support Vector Machine classifier with different sets of genes, by using ranker based feature selection methods on differentially expressed genes. Results: 414 differentially expressed genes were identified (P<0.05 by t-test) between the sunitinib response (CR+PR) and nonresponse (SD+PD) in the pts (2/3 of cohort) used as training set. The number of marker genes were reduced to 10, 15, 20, 30, 70, 100 and 150 sets based on the rank by using the Information gain and reliefF feature selection algorithms. Further evaluating these classifiers using the independent cohort (test set) yielded a 20 gene signature set (Table), as possible best clinical predictor of sunitinib response with 68.5% accuracy. The top ranking marker gene identified, AMFR, is highly downregulated in sunitinib sensitive patients. Conclusions: Gene expression profiling discriminates between sunitinib sensitive and resistant pts. AMFR gene is associated with angiogenesis, tumor cell motility, and regulates two known HIF1-α target genes (IGFB3, VCP). Studies on a larger cohort are ongoing by using PFS/OS as the clinical outcomes. Genes associated with sunitinib sensitivity Fold change AMFR -2.69 LOC283177 1.85 ERLIN2 -1.56 NUTF2 -1.92 C5orf46 -7.05 234254_at 1.63 MEX3D -2.17 THRAP3 -1.59 LPGAT1 -1.61 IQSEC3 1.62 CRIPT -1.57 SLC39A7 -1.64 KIAA1324L 1.59 LOC572558 1.51 TNRC6B 1.91 POU4F1 2.30 ATP1B1 -1.52 MCCC2 1.57 PPP3R1 -1.62 GNG4 1.58
Breast cancer stage IV from a specific city in a developing country like Colombia
Authors: J. P. Cardona Arcila, J. A. Chacon Cardona, T. Sanchez Villegas, C. R. Villegas Mejia
Journal: Journal of Clinical Oncology (2008)

12017 Background: Breast cancer stage IV is a common diagnosis in our developing countries so we follow this specific group for knowing its behavior in the Instituto Oncologico ION S.A. from Manizales with 1,000,000 people of influence. Methods: It was a retrospective analysis in the beginning from our cancer records in order to extract this specific breast cancer population and them they were follow up to December 2006. Results: The group accrued 888 breast cancer patients from January 1995 to December 2006 with 50 (5.63%) Stage IV; 100% female; median age 56 (range 32–93. sd:14.374); Urban Area 100%, Clinical symptom was mass (72%), pain (13%), best diagnoses method was test by themselves (92%), second neoplasia in 12% with contralateral breast cancer (67%) and cervical and uterus cancer with 17% each one; Ductal Carcinoma (94%), RE(+) 10%, RP(+) 8% and HER(-) 4% in only the 4% of patients, Invasion Lymph- vascular(+) 11%, MRM surgery 26%, tumorectomia or biopsy 10%, mean resected nodes 10 and mean positive resected nodes 6, familiar first degree antecedent 6%, postmenopausical stage 70%, Right breast 54%, CSE localization 42%, initial Chemotherapy (QT) scheme FAC 28%, AC 30% Doxo/Docetaxel 10% and TAC 2%; 23% changed initial QT because of pathological bad response in 8% and without clinical response with initial QT 15%; Radiotherapy 50%, Mean Tamoxifen therapy 14 months (Range 1–75 months Sd: 19.587) and 18% patients received a second hormonal therapy with Anastrazole (16%) because of relapse; general complications 20; neoadjuvant treatment 36% with QT (89%) and mixed (11%); Adjuvant Treatment 32% based on QT and RT (81%); global relapse (34%) with bony (47%), scar (12%), lung (9%), skin (6%), CNS (9%) and Liver (3%) mean follow up of 37 months (Range 1 to 123 months Sd: 35.171) and Overall Survival by Kaplan at 5 years for Breast Cancer was 34%.(CI95%: 96.3–60.8). Conclusions: This is our specific breast cancer Stage IV and its behavior with a global survival that has to be increased in next years by means of new drugs and the application of new specific Her2 drugs. No significant financial relationships to disclose.
Cinematic MRI imaging for hepatic malignancies: Implications for improving accuracy of radiation therapy.
Authors: Smith Apisarnthanarax, Annemarie Therese Fernandes, Yingshu Lin, Mark Alan Rosen, John Peter Plastaras, James M. Metz, Edgar Ben-Josef, Kevin Teo
Journal: Journal of Clinical Oncology (2014)

300 Background: Accurate radiation therapy (RT) targeting of hepatic tumors is critically dependent on organ and tumor motion assessment, most commonly performed with 4DCT. Since 4DCT captures only a snapshot of tumor motion in time and is prone to artifacts and irregular breathing, it is unclear how reliable 4DCT is in determining intra-fraction tumor motion. CineMRI allows for prolonged real-time organ and tumor motion assessment with no radiation exposure. We compared the extent of tumor motion between 4DCT and cineMRI in patients with hepatic tumors treated with RT. Methods: Sixteen patients with hepatocellular carcinoma (n=11), cholangiocarcinoma (n=3), and liver metastasis (n=2) underwent 4DCT and 2D biplanar cineMRI scans during simulation to determine the extent of target motion in the superior/inferior (S/I), anterior/posterior (A/P) and lateral directions. Biplanar cineMRI was performed over 5 minutes. Tumor motion from MRI was determined by tracking the centroid position of the gross tumor volume (GTV) using deformable image registration. Margins were determined by using histograms of 90% confidence interval of GTV motion in each direction. Motion estimates from 4DCT were performed by evaluation of the marker positions in each phase of the CT. We compared the extent of GTV motion and resulting margin size between cineMRI and 4DCT. Results: 4DCT underestimated the S/I margin in 50% of patients by a mean of 3.4 mm (range: 1.5-7 mm), the A/P margin in 44% of patients by a mean of 2.8 mm (range: 1-5.5 mm), and the lateral margin in 63% of patients by a mean of 1.6 mm (range: 0.2-4.5 mm). The average inferior motion (median to 10 th percentile) was of greater magnitude (5.0 mm vs. 3.5 mm) compared to the average superior motion (median to 90 th percentile). Superior, inferior, lateral, anterior, and posterior margins of 6, 8, 5, 6, and 4 mm respectively would be needed to cover 90% of the intra-fraction GTV motion as defined by cineMRI. Conclusions: CineMRI frequently detects larger differences in hepatic intra-fraction tumor motion when compared to 4DCT, most notably in the S/I direction, and may be useful when treating without respiratory management, particularly in patients with unreliable 4DCT imaging.
Emerging development and use of clinical pathways to improve quality and standardize care in oncology.
Authors: Colin Nash, Ken Williams, Francesca Pirog, Kristi Mitchell
Journal: Journal of Clinical Oncology (2012)

139 Background: Clinical pathways have emerged as a tool for payers to encourage provider adherence to evidence-based care. Avalere sought to understand how oncology pathway developers consider different types of evidence and physician input in designing pathways, and how the experiences of early programs may serve as an indicator for future implementation. Methods: Avalere conducted targeted white and grey literature searches to identify and analyze pathways used by oncology practice groups, provider networks, and major commercial payers. The research was augmented by informant interviews with representatives from leading organizations that have developed or implemented pathways. Results: Current pathways programs differ in their origins and objectives. Across these programs, Avalere identified findings in three key areas: Development: Developers consider efficacy of treatments first, followed by toxicity, and then cost. Many developers conduct an independent evidence review, while others leverage clinical practice guidelines. All developers solicit physician input on pathway design and updates; Use: Independent pathway developers partner with commercial insurers and large provider networks to design pathways with cost-saving components. Physicians are evaluated based on their adherence to the pathways, but are not held accountable for reporting or performance on NQF-endorsed quality measures; Impact: Cost savings in early programs are largely due to reduced toxicity-related medical costs, use of less expensive drugs, and lower total drug use. However, there is limited evidence on the impact of pathways on patient outcomes. Conclusions: There is variability across oncology pathway developers regarding their scope, granularity, and processes related to evaluating and incorporating evidence. If clinical programs demonstrate early cost reductions while improving patient outcomes, payers will likely attempt to expand pathways programs to new geographies and therapeutic areas. Existing practice patterns and previously implemented pathways programs will likely play heavily in determining which pathways are adopted in a given region, but national standardization is highly unlikely.
Outcome predictors after pneumonectomy for non-small cell lung cancer
Authors: M. El-Naghy, N. Ramnath, A. G. Antum, H. Rezaishiraz
Journal: Journal of Clinical Oncology (2005)

7274 Backgroud and Objective: The aim of this study was to evaluate the factors contributing to better survival in patients with centrally located non-small cell lung cancer who underwent pneumonectomy. Methods: This was a retrospective study based on chart review of patients with non-small cell lung cancer treated with pneumonectomy at Roswell Park Cancer Institute in the period between 1986–2002. Data was analyzed using SPSS software with Cox regression for univariate and multivariate analysis. Results: There were 220 patients identified and 160 charts were available for review and were all included for analysis. Median survival was 20 months (follow up period had a range from 12 days to 16 years), and the 5 years survival was 24%. There were 135 deaths (84.4%) during the follow-up period. The following factors impacted survival significantly: 1) Smoking had a hazard ratio (HR) of 1.41 (confidence interval (CI) = 1.01–1.99, p = 0.047). 2) Performance status (PS) of 2 and The American Society of Anesthesiologists (ASA) grade of ≥3 had HR of 3.03 (CI = 1.51–6.09, p = 0.002) and 1.79 (CI = 1.26–2.54, p = 0.001) respectively when compared to PS ≤ 1 and ASA grade ≤ 2. 3) Postoperative cardiovascular complications had a major negative impact on the outcome with HR of 6.67 (CI = 2.97–14.94, p = 0.000004). 4) Squamous cell carcinoma had a HR of 0.66 (CI = 0.47–0.94, p = 0.020) when compared to adenocarcinoma. 5) Preoperative hemoglobin level had a protective effect with HR of 0.89 (CI = 0.80–0.99, p = 0.032). 6) Higher pathological stages were associated with poorer prognosis (p = 0.037). In the multivariate model, smoking (p = 0.015), PS (p = 0.010), ASA grade (p = 0.022), and postoperative cardiovascular complications (p<0.001) were shown to independently impact prognosis. Conclusions: Smoking, PS, ASA grade, and postoperative cardiovascular complications are important independent predictors of survival after pneumonectomy for non-small cell lung cancer. No significant financial relationships to disclose.
Efficacy, Safety, and Confirmation of the Recommended Phase 2 Starting Dose of the Combination of Ruxolitinib (RUX) and Panobinostat (PAN) in Patients (Pts) with Myelofibrosis (MF)
Authors: Claire N. Harrison, Jean-Jacques Kiladjian, Florian H. Heidel, Alessandro M. Vannucchi, Francesco Passamonti, Amjad Hayat, Eibhlin Conneally, Bruno Martino, Thomas Kindler, Daniel B. Lipka, Suddhasatta Acharyya, Prashanth Gopalakrishna, Susan Ide, Tracy Liu, Song Mu, Vincent Ribrag
Journal: Blood (2015)
A phase I/II study of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer
Authors: S. R. Park, Y. S. Hong, Y. Park, N. K. Kim, Y. L. Park, S. Y. Park, K. H. Jung
Journal: Journal of Clinical Oncology (2008)

4558 Background: We conducted a phase I/II study of S-1 plus irinotecan and oxaliplatin to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) and to evaluate the efficacy and toxicity in pts with metastatic gastric cancer (MGC). Methods: Pts with MGC (+ metastatic colorectal cancer in phase I), age ≥18 yrs, ECOG PS 0–2, and adequate organ function (+ measurable lesion(s) and no prior chemotherapy in phase II) were eligible. S-1 was given twice daily, p.o. on D1–14, irinotecan and oxaliplatin i.v. on D1 every 3 weeks. In the phase I, each cohort received oxaliplatin 85 mg/m2 and escalating doses of S-1 (30–40 mg/m2 bid) and irinotecan (120–150 mg/m2). With Simon’s 2-stage minimax design, planned sample size was 44 pts in phase II. Results: In phase I, 23 pts were enrolled from Sep 2006 to Feb 2007. DLT did not occur up to the highest dose level (level 6; S-1 40 mg/m2 bid, irinotecan 150 mg/m2, oxaliplatin 85 mg/m2), and then, 5 additional pts were accrued at that level; DLT of G3 anorexia occurred in 1 pt. Although MTD was not reached, level 6 was chosen as the recommended dose for the phase II study. In phase II, 44 MGC pts were enrolled from Jun 2006 to Dec 2007; median age=54 yrs (range, 27–66); median PS=1 (range, 1–2); M/F=34/10; and the number of metastatic organ site 1/2/≥3=13/20/11. A total of 201 cycles have been administered, with a median of 4 cycles (range, 1–9+) per pt. Among 35 efficacy-evaluable pts, 2 pts had a CR (5.7%), 24 (68.6%) a PR, 7 (20.0%) SD, and 2 (5.7%) PD; the overall response rate was 74.3% (95% CI 59.8–88.8%). At a median follow-up of 3.5 mo (range, 0.1–6.3), the median TTP and OS were not reached. Updated TTP and OS will be provided at presentation. Among 42 toxicity-evaluable pts, the most common G3/4 toxicity was neutropenia (52.4% of pts) and 4 pts (9.5%) had febrile neutropenia. G3 non-hematological toxicities included diarrhea (11.9%), anorexia (7.1%), abdominal pain (4.8%), fatigue (4.8%), infection without neutropenia (2.4%), and nausea (2.4%). Conclusions: S-1 plus irinotecan and oxaliplatin is a highly active regimen with a tolerable toxicity profile as a first-line chemotherapy in MGC. Irinotecan, oxaliplatin, and S-1 were provided by Pfizer Inc., sanofi-aventis Korea, and Boryung Inc., respectively. No significant financial relationships to disclose.
Comparision of survival rates of patients (pts) with localized prostate cancer (T1-2N0M0) treated with brachytherapy (BT) and external beam radiation therapy (EBRT): Surveillance Epidemiology and End Results (SEER) database review.
Authors: Anteneh A. Tesfaye
Journal: Journal of Clinical Oncology (2013)

124 Background: Unlike in localized prostate cancer with low recurrence risk features, the role of BT in localized prostate cancer with intermediate and high risk features is not well defined. The aim of this study is to compare the survival rates of such pts treated with BT &amp; EBRT using the SEER database in the 3 different risk levels. Methods: The 1973-2009 SEER database was reviewed for men with T1-2N0M0 prostate cancer treated with radiation therapy alone between 2004-2009. Pts with additional malignancies and combination radiation therapy were excluded. Localized Prostate cancer was stratified into low (T1, T2a and PSA&lt;10 and Gleason ≤6), intermediate (T2b or PSA=10-20 or Gleason =7) and high (T2c or PSA &gt;20 or Gleason ≥8) risk for recurrence. Results: A total of 73,867 pts were retrieved from the database, of which 24,661 (33.4%) were treated with BT and 49,206 (66.6%) with EBRT. Pts treated with BT had younger median age, lower PSA, Gleason’s score, and T staging than EBRT. Five year overall survival (OS) and cancer specific survival (CSS) rates are shown in the table. On multivariate analyses, T staging, PSA level, Gleason’s score and type of radiation therapy were independent prognostic factors for 5 year CSS &amp; OS. In pts with localized prostate cancer, those treated with EBRT had 47% higher odds of dying from prostate cancer compared to those treated with BT at the end of 5 years. (HR (95% CI) =1.47 (1.113-1.94); p=0.007). Conclusions: In patients with localized prostate cancer treated with radiation alone, BT is seen to have superior 5 year OS over EBRT in all 3 risk levels. BT also has superior 5 year CSS in low and high risk levels, while being comparable in intermediate risk levels. Prospective randomized controlled trials are needed to validate this finding. [Table: see text]
A Phase 2 Clinical Trial Adding Rituximab to CODOX-M/IVAC for Untreated Burkitts Lymphoma: Correlative Analysis of Serum and CSF Rituximab Levels
Authors: Andrew M. Evens, Nahida Islam, Kenneth R. Carson, Victoria Browning, Chadi Nabhan, Borko Jovanovic, Paul M. Barr, Paolo F. Caimi, Irene Helenowski, Stephanie A. Gregory, Jill Kolesar, Leo I. Gordon
Journal: Blood (2012)
Prognostic Value of Real-Time PCR BCR-ABL Transcript Monitoring after Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia Patients.
Authors: Iwona Solarska, Miroslaw Majewski, Barbara Nasilowska-Adamska, Jan Zaucha, Iwona Kania, Hanna Makuch-Lasica, Monika Lewandowska, Grazyna Nowak, Piotr Rzepecki, Andrzej Hellmann, Bozena Marianska, Krzysztof Warzocha
Journal: Blood (2006)