tbuckley/cabot-search huggingface dataset:
Disturbed diastolic cardiac function one year after cisplatin-based chemotherapy for testicular cancer
Authors: R. Altena, J. Nuver, M. P. van den Berg, A. J. Smit, D. T. Sleijfer, J. A. Gietema
Journal: Journal of Clinical Oncology (2008)

5088 Background: Chemotherapy-induced cardiovascular effects are increasingly observed in testicular cancer (TC) survivors. Early signs of cardiovascular damage after cisplatin-based treatment are important to estimate subclinical cardiac dysfunction. We prospectively investigated changes in cardiac function within the first year after chemotherapy for disseminated TC. Methods: In TC patients (pts) treated at the University Medical Center Groningen we performed echocardiography before start of Bleomycin, Etoposide and Cisplatin chemotherapy and one year later. Systolic left ventricular function was estimated by Wall Motion Score Index (WMSI, normal =1.00); diastolic function by Tissue Velocity Index (TVI, available in 19 pts) and E/A ratio. Diastolic dysfunction was defined as TVI <8cm/s and/or E/A-ratio <1. Concomitantly cardiovascular risk factors (CRF) were assessed, including 24-hour ambulatory blood pressure (BP). Results: 42 TC pts (median age 28 years, range 18–50) were assessed pre- and post treatment. The median interval was 10 months (range 6–15). Diastolic dysfunction was present in 9 pts pre-treatment (E/A-ratio <1 n=7, TVI <8 n=1, both n=1), CRF in these 9 pts consisted of obesity (n=5) and hypertension (n=3). One year later pre-treatment diastolic dysfunction persisted in 5 pts, new dysfunction developed in 2 pts (E/A-ratio <1 n=4, TVI <8 n=2, both n=1). CRF in these 7 pts were hypercholesterolemia (n=2) and obesity (n=1). Compared with pre-treatment the median E/A ratio did not change (1.38 ± 0.46 Vs 1.35 ± 0.037; p=0.259), whereas median TVI decreased after treatment (12.0 ± 3.2 Vs 10.4 ± 2.9 cm/s; p=0.002). The median WMSI did not change (1.00 ± 0.04 Vs 1.00 ± 0.12; p=0.273). BP did not change (systolic 130 ± 11.6 Vs 122 ± 10.8; p=0.082; diastolic 74 ± 9.6 Vs 68 ± 11.4; p=0.140). Systolic BP and age correlated with TVI pre- and post treatment. Conclusions: One year after cisplatin-based treatment, TC-survivors have a significant decrease in TVI, suggesting an impaired diastolic function of the heart. Systolic parameters and BP did not change. The prognostic significance of this disturbed diastolic function 1 year after chemotherapy for future cardiovascular morbidity is not clear yet. No significant financial relationships to disclose.
Vascular anomalies in patients undergoing retroperitoneal lymph node dissection.
Authors: Andrea K. Thissen, Daniel Porres, David J. K. P. Pfister, Charlotte Piper, Axel Heidenreich
Journal: Journal of Clinical Oncology (2014)

382 Background: Anomalies of the renal vessels usually are clinically silent and might depicted during CT scanning of the abdomen for staging purposes of urological malignancies. Awareness of these rare anomalies is crucial especially in patients undergoing staging for germ cell tumors in order to avoid overstaging and unnecessary therapy. We report on the incidence of renal vessel anomalies in an unselected group of patients undergoing retroperitoneal lymph node dissection (RPLND) for testis cancer. Methods: 245 patients with testicular germ cell tumors underwent primary or secondary RPLND following inductive chemotherapy. Prior to RPLND, all patients underwent abdominal staging by CT scans or by MRI in selected cases. CT scans were reviewed with regard to the detection of vascular anomalies of the vena cava inf., renal veins, renal arteries, and iliac vessels. CT findings were correlated with intraoperative findings. Results: Overall, vascular anomalies were encountered in 39 patients (15.9%): retroaortic left renal vein in 10 (4.1%), circumaortic left renal vein in two (0.8%), reduplication of the common iliac vein in one (0.4%), accessory renal arteries in 14 (5.7%), thrombosis of the inferior vena cava in 12 (4.9%) patients with IIC disease. Anomalies of the renal vein were detected in 10 out of 12 (83%), in two cases venous anomalies were falsely diagnosed as lymph node disease in stage I NSGCT. All arterial anomalies were identified preoperatively. CT scan identified caval thrombosis in only eight cases (68%), four cases were identified by an additional MRI of the abdomen. Conclusions: Vascular anomalies are frequently encountered in patients with RPLND for testis cancer and have to be acknowledged during surgery even with negative imaging studies. Retroaortic renal veins represent a potential pitfall of CT imaging resulting in unnecessary therapy; it should be considered in pts with CT suspicious lymph nodes caudal to the renal hilus. IVC thrombosis is associated with advanced disease and is best diagnosed by MRI of the abdomen.
Detection of histone methylation on circulating nucleosomes in blood plasma
Authors: U. Deligezer, E. E. Akisik, N. Erten, N. Dalay
Journal: Journal of Clinical Oncology (2008)

14590 Background: Alterations in DNA methylation and histone modifications are implicated in carcinogenesis. Although tumor- specific alterations in DNA methylation can be detected in serum/plasma of cancer patients, no data is available on the presence of histone modifications in blood circulation. In this study, we aimed to investigate whether histone methylation, as a model of histone modifications, is detectable in blood circulation. Based on the previous demonstration that methylation at histone 3 lysine 9 (H3 Lys-9) is enriched at repetitive ALU elements, we hypothesized that if detectable in blood circulation, methylation at H3 Lys-9 should be enriched and detectable in ALU repeats when compared with a single-copy sequence (e.g. CDKN2A). Methods: Histone methylation was analyzed by chromatin immunoprecipation (ChIP) in plasma samples of patients with multiple myeloma (MM, n=21). Quantification of circulating nucleosomes by ELISA and ALU-specific DNA fragments by real-time PCR preceded ChIP providing evidence on the presence of histones and associated DNA. Results: This is the first study in the literature showing that histone methylation is detectable on circulating nucleosomes in a sequence- specific manner. In accordance with our hypothesis, the detection rate of H3 Lys-9 methylation in the ALU elements was higher than in the CDKN2A promoter (81% vs. 33.3%, respectively). In the ALU elements, we observed significantly higher levels of histone methylation compared with CDKN2A (p=0.0003). Conclusions: If validated in further studies, our findings may be the basis on investigation of cancer-specific alterations in histone modifications in the circulation. No significant financial relationships to disclose.
Young age to predict for transient elevation in PSA after definitive stereotactic body radiation therapy for prostate cancer.
Authors: Seth Blacksburg, Aaron Katz, Matthew R. Witten, Owen Clancey, Jonathan A. Haas
Journal: Journal of Clinical Oncology (2015)

118 Background: Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. There is a small body of literature characterizing a PSA bump after treatment with SBRT. Despite this, there is a paucity of data addressing rates of transient PSA increase immediately after SBRT treatment and what factors portend for this rare occurrence. This study reports outcomes on initial PSA after SBRT therapy for men who have received definitive SBRT for prostate cancer. Methods: Between May 2006 and February 2014, 921 patients with prostate cancer were treated with SBRT delivered via Cyberknife therapy. The mean age was 67 years old. 68.5% of patients were Caucasian, 17.4% African American, and 14.1% were another ethnicity. Patients were divided into prognostic risk groups with 44.7%, 43.5%, and 11.1% of patients falling in the low, intermediate, and high risk stratifications. Gleason scores were &lt; 6 in 44.4%, 7 in 41.3%, and 8-10 in 14.2%. 37 patients also received supplemental external beam radiation (median dose 4500cGy) and 8.9% of patients received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. Pre-treatment PSA was 0.8 – 205 ng/ml (median 6.1). Results: At 3 months’ follow-up, 2.8% of patients had a PSA elevated above their baseline value. 27.8% of patients age ≤50 (p&lt;.0001) and 8.4% of patients age ≤60 (p=.001) experienced an increased in baseline PSA. African Americans were more likely to experience a transient increase in PSA over Caucasians (7.8% vs. 3.0%, p=.06). Patients treated with fewer beams were also more likely have a temporary rise in PSA (p=.056). Gleason Score, Risk grouping, prostate volume, ADT, and EBRT did not predict for rise on Pearson Chi-Square analysis. On multivariate analysis, only age ≤50 (p&lt;.0001) portended for increased PSA at 3 months’ time. Conclusions: This represents the largest series evaluating elevation of PSA after definitive SBRT for prostate cancer. Temporary rise in baseline PSA after SBRT is rare. Despite that, a significant cohort of younger patients can experience transient elevation. Patient age ≤50 was found to be the only predictor of this otherwise rare occurrence.
Thalidomide alone or in combination with fludarbabine are effective treatments for patients with fludarabine-relapsed and refractory CLL
Authors: R. R. Furman, J. P. Leonard, S. L. Allen, M. Coleman, T. Rosenthal, J. L. Gabrilove
Journal: Journal of Clinical Oncology (2005)

6640 Background: CLL is characterized by an accumulation of lymphocytes due to a defect in apoptosis. CLL lymphocytes demonstrate increased NF-κB activity which may play a role in mediating resistance to fludarabine. Additionally, several cytokines have been linked to enhanced CLL survival, including TNF-α, bFGF, and VEGF. Given thalidomide’s ability to inhibit these cytokines and NF-κB activity, we investigated whether thalidomide alone or in combination with fludarabine is an effective treatment in CLL. Methods: Patients with CLL who were previously treated with fludarabine were randomized to receive either thalidomide alone (T) or in combination with fludarabine (FT). Thalidomide was started at a dose of 200 mg each night and adjusted as tolerated. Patients assigned to combination therapy started thalidomide prior to receiving fludarabine at a dose of 25 mg/m2/d x 5 days, every four weeks for a total of six cycles. Results: 16 pts have been enrolled, including 6 pts refractory to fludarabine, and randomized to receive either T (n=8) or FT (n=8). The median dose of thalidomide was 200 mg qHS (range 50–450). Of the 10 evaluable patients, there have been 1 CR (FT), 4 PRs (1T/3FT), 2 hematologic improvements (1T/1FT), 2 minor responses (1T/1FT), and one disease progression (T). Therapy was tolerated, with grade 3 toxicities being: neuropathy(2), sedation(1), thrombosis(1), febrile neutropenia(1), and infection(3). Of interest, 5 pts on T developed tumor flares, characterized by fevers, increased size and tenderness of lymph nodes, increased lymphocyte counts, and decreased hemoglobin and platelet counts. These symptoms resolved with either continued treatment (3 pts) or temporarily discontinuing the thalidomide(2 pts). Patients receiving thalidomide alone demonstrated hematologic improvement prior to achieving significant decreases in lymph node size. Conclusions: Thalidomide demonstrates activity alone and in combination with fludarabine as treatment for CLL. The combination appears to be particularly effective as treatment for patients refractory to fludarabine. The addition of F to T appears to ameliorate the development of a tumor flare. No significant financial relationships to disclose.
Changes in molecular profile following platinum chemotherapy in NSCLC.
Authors: W. Huang, M. Skokan, Y. Chang, C. Wu, J. Lee, W. Feser, A. E. Barón, P. A. Bunn, M. Varella-Garcia
Journal: Journal of Clinical Oncology (2011)

10518 Background: Platinum-based combination is the standard 1st-line chemotherapy for advanced non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKI) have shown striking treatment efficacy in in patients with specific molecular profiles. This study investigated whether the genomic profiles of NSCLC differ before and after platinum-based chemotherapy, a still pending question. Patients and Methods: Specimens from 50 stage IIIAN2, IIIB and IV NSCLC patients with diagnostic (therapy-naïve) and post-chemotherapy (paclitaxel, docetaxel or gemcitabine+cisplatin)/chemo-radiotherapy were screened by fluorescence in situ hybridization (FISH) for ALK fusions and copy number gain (CNG) of EGFR and MET . Complete results were obtained in pre- and post-treatment specimens for 45 patients. A positive marker was defined as follows: EGFR CNG: ≥4 copies in ≥ 40% cells; MET CNG: mean ≥5 copies/cell; ALK: rearrangement in >15% of the cells. Results: In diagnostic specimens, incidence of EGFR CNG (55%) was substantially higher than MET CNG (14%) or ALK+ (10%). All MET+ were also EGFR+ and all ALK+ were negative for EGFR and MET CNG. There was a significant association between EGFR CNG and female gender (p=0.001); no association was found between these biomarkers and age, smoking status, histology and stage. For ALK, there was no difference between diagnostic and post-treatment profiles in terms of presence or number of cells carrying the rearrangement (p=0.87). For EGFR and MET, no significant differences in mean copy number were detected (p=0.26 and p=0.87, respectively). However, 8 patients (18%) were classified in discordant EGFR copy number categories, 5 (10%) of which were likely due to real biological differences since similar discordance was also detected for MET. Conclusions: Platinum chemotherapy does not seem to impact occurrence of ALK gene fusions in NSCLC. Conversely, a relevant change in the copy number profile of EGFR and MET was detected in at least 10% of NSCLC, when diagnostic and resection specimens were compared. These results demonstrate variability of chemotherapy impact in molecular pathways and support that molecular testing be performed in specimens collected just prior to selecting patients for targeted therapy.
The McGill University Health Centre interdisciplinary approach to cancer pain management: Description of treatments and outcomes.
Authors: Sara Olivier, Jordi Perez, Yoram Shir, Manuel Borod, Rosemary O'Grady
Journal: Journal of Clinical Oncology (2014)

190 Background: Cancer-related symptom management is best achieved by interdisciplinary teams. In 2011, the MUHC launched an interdisciplinary Cancer Pain Clinic including palliative care, anesthesia, radiation oncology and nursing with rapid access to physiotherapy, occupational therapy and psychosocial oncology. Methods: We retrospectively analysed all new outpatients completing two subsequent visits since March 2013. Variables included a) symptom severity with the Edmonton Symptom Assessment Scale (ESAS), b) pain with the Brief Pain Inventory (BPI) and c) treatment including medication (type, formulation, dose of opioids) of non-pharmacological approaches. Results: 71 patients were analysed. Symptom management: Severity of pain and other five symptoms decreased significantly at V2 or V3 (Table). Pain significantly decreased in all four BPI categories. One third of patients had ≥50% pain relief at V2 or V3. Number of severe pain cases decreased (45% at V1 to 18% at V3) in parallel to an increase of mild pain cases (11% at V1, 41% at V3). Treatments: Acetaminophen, anticonvulsants and NSAIDs were the most common non-opioid drugs. Opioid prescription remained constant at an 80% yet the ratio between short acting (SA) and long acting (LA) changed at V3 compared to V1 (V1: SA/LA=76/44; V3: SA/LA=48/58) and the morphine equivalent daily doses decreased (V1: 100±194 mg, V2: 84±158mg and V3: 65±80mg). Among non-pharmacological methods, 28% of patients received interventional procedures, 18% psychotherapy and 12% palliative radiotherapy. Conclusions: We believe that the pain and other symptom improvement observed after three visits along with a lower opioid consumption is a result of the interdisciplinary approach offered. [Table: see text]
Identification of epigenetic aberrant promoter methylation in pleural fluid DNA is useful for diagnosis of malignant pleural effusion
Authors: H. Katayama, K. Aoe, A. Hiraki, K. Fujiwara, T. Maeda, T. Murakami, R. Eda, K. Sugi, H. Takeyama
Journal: Journal of Clinical Oncology (2005)

9567 Lung cancer and malignant mesothelioma are major cause of pleural effusion, and management of lung cancer patients with pleural effusion requires effective treatment based on timely and accurate diagnosis. Thus, differentiating between malignant and nonmalignant pleural effusions is a critical clinical problem, and conventional methods have proven to be inadequate. Aberrant methylation of CpG islands, one of the major mechanisms to inactivate tumor suppressor genes in human cancers, has been found in lung cancer and other malignancies. Recent studies revealed that detection of aberrant methylation of DNA in serum or BAL might be available to diagnose malignancies. Based on these studies, we investigated to identify aberrant promoter methylation of DNA in pleural effusion and evaluate the usefulness of this approach for differential diagnosis of pleural effusion. We examined methylation status of RARβ, p16INK4a, DAPK, RASSF1A, and MGMT in 81 pleural effusion samples using methylation-specific PCR. Forty-seven patients were given a diagnosis of malignancies (median age 69 years; range 29–87; male/female 35/12). 34 patients were non-malignant pleural effusion. In patients with malignancies, DNA methylation of pleural effusion was detected in 6.4% for MGMT, 21.3% for p16INK4a, 27.7% for RASSF1A, 29.8% for DAPK, and 40.4% for RARβ. Of 47 patients with malignancies, 34 (72.3%) had methylation of at least one gene. The total number of methylation in five genes per patient was significantly higher in malignancies (1.26 genes/patient) than in non-malignant pulmonary diseases (0.56 genes/patient, p<0.001). A crude unconditional logistic regression model correlating methylation status and risk of malignancies showed that the patients with at least one methylated gene showed 3.31 times higher probability of having mlignancies compared to patients without any methylated genes (p = 0.01). These results suggested that patients with methylation have significant high risk for malignancies,and identification of aberrant promoter methylation in pleural effusion DNA could be a useful tool for differential diagnosis of pleural effusion. No significant financial relationships to disclose.
Genomic polymorphisms of drug metabolisms associated with overall survival (OS) in advanced non-small cell lung cancer (NSCLC) treated with gemcitabine (GEM) or taxanes.
Authors: L. Zhang, C. Zhou
Journal: Journal of Clinical Oncology (2010)

7627 Background: Several polymorphisms on the genes involved in drug metabolism are known to be associated with pharmacokinetic or pharmacodynamic variability, but correlations with OS and RR have been unknown. This prospective study was investigated whether genetic polymorphisms could influence OS and RR in advanced NSCLC patients treated with third generation cytotoxic chemotherapy. Methods: Chemotherapy naïve stage IIIB or IV NSCLC patients, treated with CBDCA (AUC = 6), DDP (75 mg/m2), GEM (1,000 mg/m2), NVB (25 mg/m2), TXT (75 mg/m2) and PTX (200 mg/m2), were eligible. The DNA samples were extracted from peripheral blood mononuclear cells before treatment and SNPs of rs10999776 (SLC29A3), rs2267703 (TXSA1) and rs4149525 (SULT1E1), a category of drug metabolizing enzymes or transporters were analyzed. Statistical analyses were performed by the log-rank test and Cox proportional hazards model. Results: From Nov 2005 to Feb 2009, 342 patients (male/female: 234/108, stage IIIB/IV: 116/226, adeno/squamous/nos: 189/104/49, never-smoker/smoker: 146/196), aged 32-78 (median: 60) years, received platin-based doublet chemotherapy. The follow-up was through to 15, Jul 2009. The median progression-free survival (PFS) of 302 patients was 4.8 months, the median survival time (MST) of 342 patients was 11.5 months. Response evaluation was acceptable for 328 patients, and CR/PR/SD was 0/31.4/53.1% respectively. Of the three SNPs, there were no significant association with overall survival, but there was significant association in terms of different regiment. When treated with GEM/CIS, the OS of SLC29A3 TC was marginally longer than that of SLC29A3 TT, 17 m vs 8.1 m, respectively, p = 0.067. As for taxane-based regimen, the OS of SLUT1E1 AG and GG was 20 m and 9 m respectively, p = 0.023. Conclusions: Genes involved in the drug metabolism or elimination may be new prognostic biomarkers for patients with stage IIIB or IV NSCLC who receive GEM or PTX/TXT as the first-line chemotherapy and may unveil an unexplored molecular pathway correlated with the drug response and further may be predictive biomarkers for these patients. No significant financial relationships to disclose.
Distinctive characteristics of extrapulmonary small cell carcinoma: A Surveillance Epidemiology and End Results (SEER) analysis
Authors: J. Subramanian, V. Vamsidhar, B. W. Goodgame, R. Govindan, D. Morgensztern
Journal: Journal of Clinical Oncology (2008)

22106 Background: There are only limited data available on the clinical presentation and outcomes of patients with extrapulmonary small cell carcinoma (EPSCC). We conducted an analysis of the data reported in the Surveillance Epidemiology and End Results (SEER) to characterize the presentation and outcomes of patients with EPSCC. Methods: The study included patients aged ≥ 20 years, with small cell carcinoma (SCC) reported in the SEER database between 1973 and 2004. We compared the presentation and outcomes of patients with EPSCC to small cell lung carcinoma (SCLC). Results: 93,938 patients with SCC were identified, including 88,428 (94.1%) with SCLC and 5,510 (5.9%) with EPSCC. Median age for EPSCC was 68 years and the disease was more common in men (53%) than in women. Among the 2,374 EPSCC patients for whom staging were available, 435 (18.3%) had localized stage, 793 (33.4%) regional stage, 1,077 (45.4%) distant stage and 69 (2.9%) patients with SCC classified as localized/regional stage. For SCLC the corresponding staging distribution was 3,801 (7.1%), 17,989 (33.8%) and 31,399 (59.1%). SCC of unknown primary was the largest subgroup within EPSCC with 2,200 (39.9%) patients. Other sites involved were genitourinary 1375 (24.9%), gastrointestinal 1242 (22.5%), head & neck 327 (5.9%), breast 220 (3.9%), and endocrine 81 (1.5%). For EPSCC and SCLC, the 5-year survival for localized stage was 54.1% and 19.6% and for regional stage 31.5% and 9.7%. The 1-year survival for distant stage EPSCC and SCLC were 24.2% and 22.9%. Conclusion: EPSCC comprises a small fraction of patients with SCC. Patients with EPSCC have a higher proportion of localized stage disease compared to those with SCLC. Among patients with localized and regional stage, EPSCC is associated with better survival than SCLC. No significant financial relationships to disclose.