tbuckley/cabot-search huggingface dataset:
Review of inhaled recombinant interleukin-2 (rIL-2) in patients with renal cell carcinoma with pulmonary metastases
Authors: G. Michelson, E. Esteban, C. Garcia-Giron, A. Jimenez-Lacave, A. Canelas, P. Maroto
Journal: Journal of Clinical Oncology (2005)

4756 Background: Metastatic renal cell carcinoma has a poor prognosis, including patients with pulmonary metastases (PMRCC). The objective of this study was to obtain efficacy and safety data on inhaled rIL-2 used in clinical practice in PMRCC patients. Methods: The study was designed as a retrospective chart review in PMRCC patients being treated with inhaled rIL-2. Between 2000 and 2004, 19 centres in Spain and 2 in Portugal known to be treating such patients completed the provided patient review form. Thus, the number of patients review forms returned from centres determined the sample size (n=51). The treatment schedule was: 3 cycles of 36 MIU rIL-2 per day for 5 days/week for 12 weeks (with one week treatment free between cycles) in Spain and for 3 weeks (out of each 4 weeks) for 12 weeks in Portugal. Efficacy was assessed by best response following each treatment cycle and overall. The Kaplan-Meier method was used to estimate progression free survival (PFS) and overall survival (OS). PFS and OS were measured from the time of administration of the first dose of inhaled rIL-2 until progression, last follow up date or death, respectively. Safety data were analysed using descriptive statistics, with toxicities expressed as number of weeks, which were reported by cycle and grade. Results: At final evaluation, overall response rate (complete and partial response) was 13.7% (95% CI: 5.7–26.3%). Median PFS and OS were 8.6 (95% CI: 3.45–16.5) months and 23 (95% CI: 11.5–34.5) months, respectively. The most commonly toxicities reported were cough (40% of cycles) and fatigue (7%). The majority of weeks of toxicities were reported to be only grade 1 or 2 in severity. Conclusions: This retrospective chart review provides data, suggesting efficacy and only mild toxicity of inhaled rIL-2 in patients with MRCC compared to systemic therapy Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron
Efficacy of induction chemoradiotherapy with carboplatin and docetaxel for non-small cell lung cancer in stage III
Authors: K. Isobe, Y. Hata, K. Sugino, G. Sano, S. Sakamoto, Y. Takai, S. Sasamoto, K. Shibuya, K. Takagi, S. Homma
Journal: Journal of Clinical Oncology (2008)

18510 Background: The aim of this study was to assess the usefulness of induction chemoradiotherapy with carboplatin and docetaxel for non-small cell lung cancer (NSCLC) in stage III. Methods: The clinicopathologic efficacy in 24 patients (a mean age of 62.7(56–80), 19 men and 5 female, 14 adenocarcinoma and 10 squamous cell carcinoma, clinical stage: 16 IIIA and 8 IIIB) with clinical N2 (diagnosed under 6 mediastinoscope, 2 thoracoscope, 7 FDG-PET, 1 CT guided biopsy, and 1 TBNA) or T4 (invasion to vertebra body) who received induction therapy from April 2001 through October 2007 were evaluated. The patients who evaluated as SD or PR or CR after induction chemotherapy [2 cycles of carboplatin (AUC 6)+docetaxel (60 mg/m2) every monthly or 4 cycles of carboplatin (AUC 3)+docetaxel (30 mg/m2) every biweekly] with concurrent thoracic radiotherapy (TD 40 Gy/20 fr.), underwent surgical lung resection. Results: Total response rate of induction therapy was 83%, including down stage rate in 50%, surgical resection rate in 96% and complete resection rate in 69%. Pathologic effect was EF 1 in 9, EF 2 in 8 and EF 3 in 6. Median survival was 10.9 months in EF1 and 25 months in EF2. All EF 3 patients still alive with a mean survival of 60 months (32–76 months). From the point of survival time, there was a significant difference between EF 3 and EF 1 (p<0.05), but there was no significant difference in age, gender, PS, pathologic type, clinical stage and complete or incomplete resection. Conclusions: Pathologic effect was correlated with prognosis after induction therapy in stage III NSCLC. No significant financial relationships to disclose.
Genome-wide profiling of histone 3 lysine 36 trimethylation in clear cell renal cell carcinoma.
Authors: Thai Huu Ho, Jeong-Heon Lee, Rafael Nunez Nateras, Erik P. Castle, Melissa L. Stanton, Richard Wayne Joseph, Alan H. Bryce, Estrella M. Carballido, Alexander S. Parker, Zhiguo Zhang, Tamas Ordog
Journal: Journal of Clinical Oncology (2014)

464 Background: Although the von Hippel-Lindau (VHL) tumor suppressor gene is mutated in 60% of ccRCC, deletion of VHL in mice is insufficient for tumorigenesis. Sequencing of ccRCC tumors identified mutations in SETD2, a histone H3 lysine 36 (H3K36) trimethyltransferase. We hypothesize that loss of SETD2 methyltransferase activity alters the genome wide pattern of H3K36 trimethylation (H3K36me3) in ccRCC, and contributes to the cancer phenotype. Methods: To generate a genome-wide profile of H3K36me3 in frozen nephrectomy samples and RCC cell lines, we optimized a chromatin immunoprecipitation (ChIP) protocol for the isolation of DNA associated with H3K36me3. H3K36me3 is associated with open chromatin and an H3K36me3-specific antibody was used for immunoprecipitation of endogenous H3K36me3-bound DNA. ChIP PCR primers were optimized for active genes, such as actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a “gene desert” on chromosome 12 (negative control). ChIP libraries were then generated from 3 paired uninvolved kidney and RCC and 2 RCC cell lines. In order to identify H3K36Me3 upregulated regions in uninvolved kidney and RCC, reads from the ChIP sequencing were mapped to the human genome using Burrows-Wheeler Aligner and SICER algorithms. Results: Using ChIP PCR, we found that active genomic regions were enriched 15-30 fold over the negative controls indicating that the quality and yield of immunoprecipitated DNA/chromatin complexes from frozen tissue was sufficient for ChIP sequencing. A preliminary ChIP sequencing analysis of RCC cell lines and frozen ccRCC tissue indicates that H3K36me3 enriched DNA sequences were mapped to exons (31.3%) compared to introns (13.5%, p&lt;0.001), consistent with the role of H3K36me3 in transcription. Conclusions: Genomic regions enriched for H3K36Me3 binding were identified from patient-derived tissue and RCC cell lines. Current efforts are focused on comparing the H3K36me3 profiles between matched tumor and uninvolved kidney ChIP libraries to generate a genome wide map of dysregulated H3K36me3 modifications.
Radiation therapy sequencing for resected pancreatic adenocarcinoma in the National Cancer Data Base: A multi-institutional comparative analysis.
Authors: Lauren E Colbert, William A Hall, Dana Nickleach, Yuan Liu, Jeffrey M Switchenko, Theresa Wicklin Gillespie, Joseph Lipscomb, David A. Kooby, John S. Kauh, Jerome C. Landry
Journal: Journal of Clinical Oncology (2013)

305 Background: Pancreatic adenocarcinoma (PAC) remains a devastating malignancy and the role for preoperative radiation therapy (prRT) remains uncertain. This analysis used the National Cancer Data Base (NCDB) to report outcomes for the largest known retrospective cohort of patients treated with prRT for resectable PAC to date. Methods: NCDB data were obtained for all patients who underwent resection and RT for PAC from 1998-2002. Patients with metastatic (M1) disease, combined prRT and poRT, missing OS or missing RT variables were excluded. The difference in patients’ characteristics was assessed by a Chi-square test and ANOVA. The Kaplan-Meier method was used to estimate overall survival (OS); survival differences were assessed using a log-rank test. A Cox proportional hazards model was used for unadjusted and multivariable (MV) survival analysis. Two MV logistic regression models also were used to assess for differences in margin status and lymph node (LN) status across treatment groups. Results: 5,414 analyzable patients were identified. 5.1% (277/5,414) received prRT and 94.9% (5,137/5,414) received poRT. All patients underwent resection and prRT or poRT +/- chemotherapy; 92.9% chemo. 793 patients were AJCC 5 th edition stage I, 1,002 stage II, 2,990 were stage III, and 522 were stage IVa; 107 patients were M0 with unknown overall stage. There was no significant difference in OS between the two groups on unadjusted Kaplan-Meier analysis. In covariate-adjusted analysis, there was no significant difference in OS in the prRT (HR, 1.20 [95% CI .98-1.48]; p = 0.08) compared with poRT; prRT was associated with lower rates of LN positivity (OR, 0.45 [95% CI 0.31-0.65]; p &lt; 0.001) and higher rates of negative margins (OR 1.71 [95% CI 1.17-2.52]; p = 0.006). Conclusions: In the largest published series of prRT patients to date, prRT was associated with negative margins and LN negativity at resection. There was no significant difference in OS between the groups. Limitations of this study include its retrospective nature, a small prRT cohort and lack of comorbidity data. These data may be useful in generating future prospective studies of prRT for PAC.
The Biologic Meaning of the Structural Components of Defibrotide (DF) in the Setting of HIV Disease with Refractory Herpes, Candida, Cryptosporidium Diarrhea and Multi-Organ Failure Against the Background of Down-Regulation of Cellular Immunity, Autocrine Upregulation of Inflammatory Cytokines of TNF-Alpha, IL2, IL1, IL6 and Dysregulation of cAMP/cGMP Protein Kinase A/C Signalling.
Authors: Arsinur D. Burcoglu-Oral
Journal: Blood (2007)
Long-term clinical and toxicity outcomes of hypofractionated intensity-modulated radiation therapy for clinically localized prostate cancer.
Authors: Rupesh Kotecha, Michael A. Weller, Gaurav Marwaha, Jason Hearn, Patrick Kupelian, Chandana A. Reddy, Jay P. Ciezki, Kevin L. Stephans, Rahul D. Tendulkar
Journal: Journal of Clinical Oncology (2014)

49 Background: As an alternative to dose-escalated conventionally fractionated radiotherapy, hypofractionation capitalizes on the unique radiobiology of prostate cancer cells. This study reports the long-term clinical outcomes and late treatment-related toxicities in patients with clinically localized prostate adenocarcinoma treated with hypofractionated radiation therapy at a single tertiary-care institution. Methods: Between 1996 and 2008, 822 patients were treated with hypofractionated intensity modulated radiation therapy (IMRT) (70 Gy in 2.5 Gy/fraction) directed to the prostate gland with or without coverage of the seminal vesicles over a 5.5 week period. Actuarial rates of biochemical relapse free survival by the nadir + 2 definition (bRFS), distant metastasis free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity outcomes were available and measured according to the National Cancer Institute Common Toxicity Criteria (v3) in 773 (94%) of the patients. Results: The median follow-up was 8.5 years (range: 0-14.2 years). The overall 10-year bRFS, DMFS, and OS rates were 69.6%, 86.4%, and 71.7%, respectively. By National Comprehensive Cancer Network (NCCN) low-, intermediate-, and high-risk groups, the 10-year bRFS rates were 86.9%, 74.1%, and 41.3%, respectively. The rate of grade 2 or worse late genitourinary (GU) and gastrointestinal (GI) toxicity rates were 17.2% and 5.6 %. Only 1.4% of patients experienced late equal to or greater than grade 3 GU toxicity and 1.0% experienced late greater than or equal to grade 3 GI toxicity. Of those who had any toxicity during the follow-up period, 47% and 65% of patients experienced resolution or improvement in their GU and GI symptoms, respectively. Conclusions: Hypofractionated IMRT for localized prostate cancer provides excellent long-term relapse-free survival rates that are comparable to historical studies using conventional fractionation. With modern IMRT and image guidance, HFRT has an acceptably low incidence of late GU and GI toxicities, and appears to be a suitable treatment alternative to conventional fractionation.
Emotional well-being and quality of life in patients undergoing radiation therapy for pancreatic and hepatobiliary malignancies.
Authors: B. T. Samuelson, E. K. Fromme, J. Waller, C. R. Thomas
Journal: Journal of Clinical Oncology (2011)

297 Background: Therapy for GI malignancies has long been known to have a marked impact on quality of life, yet this relationship remains poorly understood. The specific aim of this analysis was to evaluate the impact of radiation therapy (RT) on emotional well-being and QOL in patients receiving RT for pancreatic and hepatobiliary malignancies. Methods: A retrospective, IRB-approved chart review was performed of 722 patients receiving RT for any cancer diagnosis between 1/1/2006 and 12/31/2008. Subjects completed the Functional Assessment of Cancer Therapy General (FACT-G) questionnaire before and after RT. Pre- and immediately post-RT course scores were compared using student t-tests with Bonferroni correction for multiple comparisons (7 comparisons, alpha =.007). Results: 722 of 1369 (52.7%) patients participated in the Patient Related Outcome database. Complete pre and post RT spirituality data were available for 73 (64.6%) patients with GI malignancies, including 24 (33%) with pancreatic or hepatobiliary disease. Average age was 61, 15 (63%) were male and 14 (58%) received definitive treatment. A decrease in both functional and physical well-being was demonstrated in post-RT scores as compared to pre-RT. Emotional well-being, however, increased (17.60 to 18.72, p=0.051), a trend not replicated in any of the other GI malignancies. Further analysis demonstrated this improvement was largely due to a decrease in positive response to the statements “I feel nervous” (1.21 to 0.67, p=0.009) and “I worry my condition will get worse” (1.58 to 1.25, p=0.043). A decrease in positive response to “I feel sad” and an increase in positive response to “I am satisfied with how I am coping with my illness” were also noted, but differences were not significant. Conclusions: Emotional well-being of those receiving RT for pancreatic and hepatobiliary malignancies appears to improve over the course of therapy, even while other measures of QOL decline. Additional investigations in larger populations are warranted to further elucidate this relationship. Documentation of PROs may have potential for impact on QOL for patients with these and other malignancies. No significant financial relationships to disclose.
Surgeon volume and disparities in post-operative complications among black men.
Authors: Ramdev Konijeti, Nedim Ruhotina, Stephen Reese, Benjamin I. Chung, Adam S. Kibel, Steven L. Chang
Journal: Journal of Clinical Oncology (2014)

66 Background: Racial and ethnic disparities related to prostate cancer treatment are well-described. Lower rates of postoperative complications are noted in men who undergo radical prostatectomy (RP) at high-volume centers or by high-volume surgeons. We assessed whether access to high-volume providers might account for ethnic disparities in postoperative complications from RP. Methods: Using a nationally representative dataset of hospital discharge information, the Perspective Database (Premier Inc, Charlotte, NC), we examined all men who underwent RP (ICD9 60.5) between 2003 and 2010. Data were stratified based on patient characteristics (age, race, marital status, insurance status, Charlson Comorbidity Index), hospital characteristics (number of beds, teaching vs. nonteaching, urban vs. rural, and geographic region), surgical approach (robotic vs. nonrobotic), surgeon volume (low [less than 5], intermediate [5 to 24], and high [more than 24]), and complications (based on Clavien classifications I-V), if any. A logistic regression model accounting for clustering &amp; survey weights was constructed to assess the association of surgeon volume &amp; ethnicity on postoperative major complications (i.e., Clavien III-V). Results: In a multivariate model incorporating clinicodemographic and hospital information, black men continued to demonstrate a higher odds for major complication (OR 1.3 [1.02-1.7]). However, when further incorporating surgeon volume to the multivariate model, there was no longer any difference in the odds for a major complication for black men (OR 1.2 [0.97-1.6]). Patients who underwent RP by intermediate-volume surgeons and high-volume surgeons had a lower incidence of postoperative major complications compared to those treated by a low-volume surgeon (OR 0.6 [0.5-0.7] &amp; 0.4 [0.3-0.5], respectively). Compared to white men, the odds of undergoing RP by a high-volume surgeon are lower for black men (OR 0.6 [0.5-0.8]). Conclusions: Our data demonstrate that access to high-volume surgeons may explain the increased odds for postoperative major complications among black men undergoing RP. Further research related to barriers to health care access &amp; further efforts at removing said barriers for black men is warranted.
Gemcitabine chemotherapy until symptomatic disease progression in advanced pancreatic cancer: A retrospective analysis.
Authors: Yuk Ting Ma, Syed A. Hussain, Philip James Johnson, Daniel H. Palmer
Journal: Journal of Clinical Oncology (2012)

372 Background: Gemcitabine was established as the standard first-line therapy for patients with advanced pancreatic cancer in 1997 after a randomized phase III study showed a statistically significant improvement in clinical benefit response and a modest improvement in median survival time, compared to bolus 5FU chemotherapy. The natural history of advanced pancreatic cancer is characterised by the rapid and relentless progression of tumor-related symptoms, thus we have analysed the outcome of our patients with advanced pancreatic cancer who have been treated with gemcitabine until symptomatic disease progression, without the use of regular radiological assessment. Methods: A retrospective analysis was conducted on all patients with advanced pancreatic cancer who were treated with first-line gemcitabine chemotherapy between January 2008 – December 2009. Results: A total of 50 patients were identified (21 with locally advanced disease, 29 with metastatic disease). The overall median survival was 10.4 months (11.3 months for patients with locally advanced disease, 7.2 months for patients with metastatic disease). Conclusions: Our single centre experience suggests that clinical decision-making based on symptomatic disease progression in advanced pancreatic cancer, results in survival outcomes that are comparable to published trial data.
Significance of serum <i>N</i>-glycan profiling as a diagnostic marker in testicular germ cell tumor.
Authors: Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2016)

489 Background: Specific tumor marker for seminoma is still lacking. Moreover, 10% to 15% of the patients with non-seminomatous germ cell tumor (NSGCT) can be expected to have normal marker levels. Glycan-based biomarkers for testicular germ cell tumor (TGCT) have not yet been established. We examined whether the serum N-glycan profiling can be applied to detection in patient with TGCT. Methods: We performed a N-glycan structural analysis of sera from 14 patients with GCT and age-matched 28 healthy volunteers using the glycoblotting methods and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The intensity of the N-glycans was compared between the TGCT patients and the volunteers to select TGCT associate N-glycans. Optimal cut-off values were determined by receiver operating characteristic (ROC) curves. Selected N-glycans were divided according to cut-off values, and positive numbers of TGCT associated N-glycan was added up to risk classification. Results: Six (43%) had seminoma, and eight (57%) patients had NSGCT in this study. The numbers of patients in stage I, II, III were 5, 2, and 4, respectively. Three patients had extragonadal tumor. The numbers of patients in IGCCC good, intermediate and poor risk were 10, 1, and 3, respectively. There were 3 patients (21%) with negative in any tumor markers. We identified 70 kinds of N-glycans in sera from healthy volunteers and GCT patients. A total 6 of N-glycans; m/z 2336.85, 2378.86, 2890.05, 3195.16, 3341.22, 3560.30 were selected as significantly high intensity in the patient with TGCT than in the healthy volunteers, with the area under the curve (AUC) of 0.81, 0.83, 0.86, 0.84, 0.81, and 0.78, respectively. Tumor associated N-glycans were classified as positive or negative, and scored from 0 to 6 points. Optimal cut-off score for detection was determined by ROC curve, and score &gt; 3 were selected (AUC 0.90, P &lt; 0.001). Based on this classification, 2 of 3 patients with negative tumor markers were categorized as a carrier for TCGT. Conclusions: Although the present study is small and preliminary, serum N-glycan analysis is a potential approaches to discover new biomarkers for TGCT. Further validation study is warranted.
Association of radiologically defined hepatosteatosis and colorectal cancer liver metastases.
Authors: Adrian D. Parasca, Timothy E. O'Brien
Journal: Journal of Clinical Oncology (2013)

367 Background: Non alcoholic fatty liver disease (NAFLD) is common, with a prevalence estimated at 15-35%. NAFLD was found to be an independent risk factor for colorectal cancer (CRC). The relationship between CRC and metastasis to a fatty liver has not been well established. We performed a retrospective chart review to address the association of radiologic hepatosteatosis and liver metastases in patients with CRC. Methods: Medical records of 291 patients diagnosed with colorectal adenocarcinoma between 2006-2010 at MetroHealth Medical Center were reviewed. Patients with CRC and no abdominal imaging within 3 months of diagnosis were excluded. Demographic and tumor related data were collected. Presence of hepatic steatosis was defined by radiographic reports (CT, MRI, or US). Results: 6/38 (18.8%) patients with hepatosteatosis had liver metastases, compared to 60/253 (23.7%) with no steatosis. The difference did not reach statistical difference (p=0.40). Hepatosteatosis was noted in 27/280 (9.6%) contrasted CTs, 4/42 (9.5%) MRIs and 12/54 (22.2%) U/S. 66 (22.7%) patients had liver metastases. Patients with ≤3 metastases were less frequent in the non-fatty 22/59 (37.3%) vs fatty liver group 3/6 (50%), but this was not statistically significant (p=0.67). Fatty liver patients were more likely to have a stage ≤ II compared to non-fatty liver patients (OR 2.40, p=0.018). Patients with hepatosteatosis had a higher mean BMI (32.8 vs 27.6, p&lt;0.001). BMI was an independent predictor of steatosis. Alcohol consumption was not associated with BMI or steatosis. There was no statistically significant difference between racial groups and gender with respect to steatosis and liver metastases. Conclusions: This retrospective study suggests that liver metastases in CRC patients are less common in those with fatty livers compared to those with non-fatty livers. CRC patients with hepatosteatosis were also more likely to have earlier stage disease. Larger studies are needed to confirm these findings.