tbuckley/cabot-search huggingface dataset:
Role of anticoagulation (AC) in patients with advanced pancreatic cancer (APC) with splanchnic venous thrombosis (SVT).
Authors: S. P. Kar, P. Bhosale, M. J. Overman, J. Weatherly, L. Xiao, R. A. Wolff, M. M. Javle
Journal: Journal of Clinical Oncology (2011)

e14622 Background: SVT is a known complication of APC. However, its natural history and management remain poorly characterized. Methods: APC patients (pts) with SVT identified on Computed Tomography (CT) imaging were included. All baseline and follow up CT scans were reviewed by study radiologist (PB). Thrombus site, type and progression on follow up were recorded. Survival was calculated from the date of diagnosis of SVT. Survival analysis used the log-rank statistic stratified for stage of APC; Chi-square and Fisher’s exact methods were applied for appropriate variables. Results: 81 pts included (median age 66 years, 54 male, stage 2/3/4=8/23/50; treatments: chemotherapy 96%, radiation 37%). Primary sites of SVT were portal (49%), superior mesenteric (27%) and splenic (23%) with 36% having >1 vein involved. Of the SVTs, 56% were tumor thrombi and 51% had complete occlusion; 48% received anticoagulation (90% low molecular weight heparin, 10% warfarin). Site and number of thrombosed veins did not affect survival (p=NS, stratified by AC). SVT complications were nonmalignant ascites 49%, varices 19%, splenomegaly 17% and bowel ischemia/edema 9%. Progression of thrombus on follow up CT was associated with above SVT complications (p<0.01). On univariate analysis, median survival in pts with ascites vs those without was 23 vs 38 wks (p=0.09). Minor bleeding was the only adverse event attributable to AC (7%). Conclusions: Progressive SVT in APC is associated with an increased rate of complications and poor survival. AC in this setting is safe and may reduce risk of SVT-related ascites but its impact on survival is unproven. Complication Median survival (stages 3+4, wks) P value AC Non-AC Ascites 41 15 0.07 Varices 46 26 0.5 Splenomegaly 49 14 0.6 Bowel ischemia/edema 15 9 0.09 Overall 38 26 0.5 Thrombus progression on CT 18% 33% 0.1
Tumor genomic profiling of FFPE samples by massively parallel sequencing.
Authors: N. Wagle, M. F. Berger, M. J. Davis, B. Blumenstiel, M. DeFelice, W. C. Hahn, M. Meyerson, S. B. Gabriel, L. E. MacConaill, L. A. Garraway
Journal: Journal of Clinical Oncology (2011)

10502 Background: Knowledge of tumor genetic alterations that may predict therapeutic response represents a growing translational need. Here, we describe a massively parallel sequencing platform to detect salient genetic alterations in formalin-fixed paraffin embedded (FFPE) tumor samples. Methods: We designed ~7000 hybrid capture baits corresponding to all exons from 138 cancer genes. Barcoded sequencing libraries were made using genomic DNA from FFPE tumor material. Equimolar pools were subjected to solution-phase hybrid capture followed by massively parallel sequencing (Illumina). Sequencing data was deconvoluted and genomic alterations were identified. Results: Hybrid capture and sequencing was performed on genomic DNA from 10 FFPE breast and colon cancer samples and 2 control DNAs. Each sample was evenly represented (mean coverage = 102x). 125 single nucleotide variants, 17 small insertions/deletions, and 47 copy number alterations were seen. These included known somatic mutations in KRAS and PIK3CA; nonsense mutations in tumor suppressors APC, MSH2, SMAD2, SMAD4, TSC1, and TP53; and a 2bp deletion in BRCA1. Amplifications were seen in CDK8, Cyclin D1, FGFR1, GNAS, MYC, and SRC. Several alterations suggested novel therapeutic approaches, including mutations in PIK3CA (PI3K inhibitors), TSC1 (TOR inhibitors), BRCA1 (PARP inhibitors) and amplification of FGFR1 (FGFR inhibitors). We also profiled these samples using a genotyping platform that assays 450 mutations in 35 genes (“OncoMap”). We detected 12 mutations across the 10 FFPE samples, 11 of which were also identified by sequencing (the 12th was visible by manual review). OncoMap failed to detect 3 mutations found by sequencing; these were confirmed by direct genotyping. Conclusions: We have developed a targeted, massively parallel sequencing platform to detect genomic alterations in archival tumor samples. This method detects base substitutions, amplifications, and deletions with high accuracy as compared to other methods in clinical use, at a comparable cost. This approach may facilitate individualized approaches to cancer treatment by identifying “actionable” genetic changes in each patient’s tumor, thereby speeding the advent of personalized cancer medicine.
Efficacy of carboplatin and paclitaxel therapy in patients with advanced squamous cell carcinoma (SCC) of the anal canal.
Authors: Jennifer Byer, Amit Mahipal, William R. Dinwoodie, Khaldoun Almhanna, David Shibata, Richard D. Kim
Journal: Journal of Clinical Oncology (2013)

539 Background: Development of distant metastases in SCC of the anal canal is not very common after treatment with combined modality. Only widely published data for treatment of metastatic disease is cisplatin and 5-FU. Carboplatin and paclitaxel is commonly used in squamous cancer of the lung but its efficacy in SCC of the anal cancer is unclear. The objective of this study is to determine the tolerability and outcome of patients with SCC of the anal canal treated with carboplatin/paclitaxel at Moffitt Cancer Center. Methods: Retrospective analysis was conducted looking at Moffitt Cancer tumor registry from 1/2007 to 1/2012. Eligible patients were required to have diagnosis of SCC of the anal cancer and received carboplatin/paclitaxel every 3 weeks as part of the treatment. Results: 13 patients fulfilled the criteria. 11 patients were initially diagnosed with early stage (Stage I-III). 11 patients received concurrent chemo radiation (Nigro regimen or cisplatin + 5-FU) and had reoccurrence. 2 patients were initially diagnosed with Stage IV disease. Median age was 56 years and 77% were females. Upon diagnosis of metastatic disease, 11 patients received prior chemotherapy (cisplatin/5FU, irinotecan/cetuximab, cisplatin/docetaxel). 4/13 patients received 2 prior chemotherapy regimens, 7/13 received only 1 prior regimen and 2/13 did not receive any prior chemotherapy. Patients received an average of 4.7 cycles (1 cycle= 3 weeks). Median was 4 cycles. The response rate was high at 62% with 2 patients achieving complete response and 6 patients with partial response. Grade 3 toxicities included peripheral neuropathy (n= 3), diarrhea (n= 1), and infection (n=3). 4 patients had grade 3 neutropenia and 1 patient had grade 4 anemia. Median progression free survival and overall survival were 4.6 and 10.5 months respectively. Conclusions: Carboplatin and paclitaxel seem to be well tolerated and have activity in the treatment of advanced SCC of the anal canal. Larger studies need to be conducted to validate these findings.
Measurement of Pax2, TC21, CCND1, and RFS1 as predictive biomarkers for outcomes in the NCIC CTG MA.12 trial of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer.
Authors: M. Basik, D. Keilty, O. Aleynikova, D. Tu, X. Li, L. E. Shepherd, V. Bramwell
Journal: Journal of Clinical Oncology (2011)

560 Background: Several molecular factors have been associated with the sensitivity of breast cancers to tamoxifen (T). Pax2 can mediate the repression of ERBB2 expression by the tamoxifen-ER complex; TC21 is a member of the RAS superfamily associated with increased recurrence in tamoxifen-treated patients; CCND1 (Cyclin D1) is frequently amplified in breast cancers; and RSF1is frequently co-amplified with CCND1 on chromosome 11q. Here we sought to validate the predictive value of each of these biomarkers in the MA-12 randomized study of T vs placebo (P) in early premenopausal breast cancer. Methods: Premenopausal women with node (N) +ve/high risk N -ve early breast cancer, any H status, received standard adjuvant chemotherapy and then were randomized to T (20 mg/day) or P for 5 yrs. Overall survival (OS), relapse-free survival (RFS) were evaluated. A tissue microarray containing biopsies of 492 breast tumors (73% of patients) was used. Immunohistochemistry was used for Pax2 and TC21, while FISH was used to measure CCND1 and RSF1 copy number. To assess the effect of these biomarkers on OS and DFS we used a multivariate Cox model to obtain hazard ratios (HR) adjusting for factors considered in the main trial. Results: 672 women were accrued and followed for a median of 8.4 years. We successfully measured Pax2 in 452 pts, TC21 in 450 pts, CCND1in 448 pts and RSF1 in 410 pts. Pax2 or TC21 expression were not associated with OS or RFS in either arm of the trial. However, in the ER+ subgroup, there was a trend so that pts with low TC21 expression (34%) derived greater RFS benefit from T compared with P(HR 0.44; 95% CI 0.20-0.95) than patients with high TC21 expression (HR 1.02; 95% CI: 0.63-1.66)) (interaction p= 0.08). No statistically significant interaction with treatment was observed with either CCND1 or RSF1 amplification, although the 6.8% of pts with high RSF1 copy number showed a trend towards no benefit from tamoxifen (interaction p= 0.09). Conclusions: Although none of the 4 biomarkers for tamoxifen response were validated in this clinical trial, the predictive effect of TC21 expression and RSF1 amplification deserve further study.
Effectiveness of darbepoetin alfa administered every three weeks to elderly patients with chemotherapy-induced anemia
Authors: J. M. Gasent, J. C. Bermejo, P. López, M. Doménech, P. Sánchez-Rovira, K. Villadiego, C. de Pedro, P. Iturralde, J. A. Gasquet, C. A. Rodríguez
Journal: Journal of Clinical Oncology (2008)

20690 Background: There are few studies specifically assessing, within routine clinical practice, the treatment of chemotherapy-induced anemia (CIA) in the elderly. The objective of this study was to describe the efficacy and safety of darbepoetin alfa (DA) administered once every 3 weeks (Q3W) in this patient population. Methods: This was a prospective, single-arm, multicenter study in 28 Spanish centers. Eligible patients (pts) were ≥65 yrs, with non-myeloid malignancies, anemic (hemoglobin [Hb]≤11g/dL), and scheduled to receive ≥9 weeks (wks) of chemotherapy. Pts were treated with a fixed dose of DA 500mcg Q3W and treatment stopped if Hb levels exceeded 13g/dL. Primary endpoint was hematopoietic response (Hb increase ≥2g/dL or Hb ≥12g/dL in absence of transfusions in the previous 28 days). Secondary endpoints included percentage of pts achieving target Hb (>11g/dL without red blood cell transfusion within 28 days), changes in the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) scale, and the incidence of adverse reactions. Results: This planned interim analysis included 75 pts (mean age 73.7 years, median weight 68kg, 68.9% with ECOG Performance Status (0–1), 60% women). 60% of pts had solid tumors and 40% lymphoproliferative malignancies; 70.6% of pts had stage III/IV. Most pts (88.0%) had baseline Hb levels between 9–11g/dL. DA was administered for a median of 7.0wks (range: 1–19). The Kaplan-Meier estimate (KM; 95% CI) for pts who achieved hematopoietic response was 65.5% (48.4–82.6) and 73.5% (49.8–97.2) for pts who achieved target Hb (>11g/dL). The FACT-F score in pts who increased Hb between wk 0 and EOTP was 3.4 points compared with -3.7 points for pts with no increase in Hb levels. One pt (1.3%) had an adverse reaction (urticaria). Conclusions: 500mcg DA Q3W for the treatment of CIA in elderly patients appears to be effective and safe. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen
Risk of cerebral metastases for postoperative locally advanced non-small cell lung cancer
Authors: S. Wang, X. Ye, W. Ou, Y. Lin, B. Zhang, H. Yan
Journal: Journal of Clinical Oncology (2008)

8113 Background: Cerebral metastases contribute most to the failure of locally advanced non-small cell lung cancer (NSCLC) management. Implications of prophylactic cranial irradiation (PCI) for locally advanced NSCLC are still controversial. Our study assessed the risk factors of brain metastases in patients with postoperative locally advanced NSCLC. Implications for PCI are discussed. Methods: 233 patients treated with surgical resection for stage III-N2 NSCLC were retrospective analyzed. To find out the risk factors of brain metastases in patients with locally advanced NSCLC, and establish the mathematical model. Results: Median survival for the entire patient was 28 months. The overall survival at 1, 2, and 3 years was 84.3%, 56.9%, and 44.8%, respectively. Brain metastases rate for the entire patient was 38.1% (85/223). Brain metastases rate for patients with single mediastinal lymph-area metastases at 1, 2, and 3 years was 6.8%, 12.8%, and 16.6%, respectively. And brain metastases rate for patients with multiple mediastinal lymph-area metastases was 31.1%, 55.5%, 61.1%, respectively (P=0.000). There was significant difference in brain metastases rate among patients with mediastinal metastasis number less than 4, 4 to 6, and more than 6 (P=0.000). Brain metastases rate for the patient with squamous cell histology at 1, 2, and 3 years were 10.1%, 21.7%, and 24.6%, respectively. But for those with nonsquamous NSCLC were 19.5%, 33.8%, and 39.0%, respectively (P=0.013). Conclusions: Risks of cerebral metastases for postoperative locally advanced NSCLC were nonsquamous cell histology, multiple mediastinal lymph-area metastases, and multiple lymph node metastases. Mathematical model of brain metastases risk was established, logit (P) = 8.215 - 0.903 * (number of metastases lymph node) - 0.872 * (Surgical resection evaluation) - 0.714 * (histology) - 1.893 * ( metastases degree) - 0.948 * (TNM-stage) - 1.034 * (adjuvant chemotherapy).P-value≥0.44 referred as brain metastases risk was high, and may referred as implication for PCI in locally advanced NSCLC clinical trials. No significant financial relationships to disclose.
Defining the molecular tumor margin regions of clear cell renal carcinoma tissues by MALDI-MS imaging of lipid and glycan species.
Authors: Richard Drake, Thomas Powers, Ellen Jones, Anand Mehta, Raymond S. Lance, Dean A. Troyer
Journal: Journal of Clinical Oncology (2013)

421 Background: The frequent tumor recurrence associated with clear cell renal cell carcinoma (ccRCC) suggests that there are underlying molecular processes present in the remaining tissue following nephrectomy that are not identified through conventional histopathological techniques. At the molecular level, transcript, metabolomic, and protein expression patterns have indicated a striking Warburg Effect profile in ccRCC tissues, with major affects on sugar and lipid metabolism. Our group has been applying MALDI mass spectrometry imaging approaches to uniquely profile lipids and glycans associated with disease progression directly in frozen tissue slides. Methods: Frozen ccRCC tissues with tumor, non-tumor adjacent, and tumor margin regions were selected by a pathologist. Lipid profiles from fresh-frozen tissue slides coated in DHB matrix were obtained on a dual source Bruker Solarix 70 FTICR mass spectrometer. Glycans were imaged in a similar fashion in ethanol-washed tissues using on-tissue protein N glycanase F digestion to release surface N-glycans. Detected lipid and glycan ion intensities were converted to a color pixel scale for creating an image of individual peaks, linked directly to the histopathology of the tissue. Results: Five groups of lipid and N-glycan species were identified following MALDI tissue imaging, those present in the immediate margin area of non-tumor tissue adjacent to tumor; only in non-tumor regions; only in tumor regions; primarily in tumor regions but extended beyond the margin; and present throughout the tissue. Specific lipid and glycan species associated with margin and tumor regions are being correlated with disease progression and pathology data. Conclusions: Analysis of the periphery of the tumor tissue and the normal parenchyma or capsule regions at this biomolecule level may better define the metastatic potential of the tumor as compared to analysis of the central tumor region. This approach has the potential to not only improve prognostic assessment and treatment choices, but also to inform on the underlying biology of ccRCC metastasis and new rational targets for therapeutic intervention.
Granulocytic and Monocytic Myeloid-Derived Suppressor Cells May Have Different Role on Allogeneic Stem Cell Transplant Outcomes
Authors: Sung-Eun Lee, Ji-Young Lim, Da-Bin Ryu, Tae Woo Kim, Young-Woo Jeon, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, Woo-Sung Min, Chang-Ki Min
Journal: Blood (2015)
Whole pelvic irradiation for prostate cancer patients with a biochemical relapse following radical prostatectomy: The era of robot-assisted minimally invasive surgery.
Authors: Jae-Sung Kim, Hyun-Cheol Kang, Seok-Soo Byun, Sang Eun Lee
Journal: Journal of Clinical Oncology (2014)

210 Background: We hypothesized that the addition of whole pelvic radiotherapy (WPRT) might improve biochemical outcome in salvage radiotherapy (RT) for biochemical failure (BCF), especially in patients with postoperative high-risk features after radical prostatectomy (RP) being good candidates beneficial from WPRT. Methods: From August 2004 to April 2012, 180 patients who experienced BCF after RP were treated with salvage RT. The primary end point was the biochemical relapse-free survival (bRFS) defined as no prostate-specific antigen (PSA) failure and no additional salvage treatments. Patients were stratified into theee groups; prostate bed radiotherapy (PBRT) alone (n = 52), PBRT with hormone (n = 85), and WPRT with hormone (n = 43). The effects of WPRT combined with hormone was measured in the high-risk patients defined as pN1 stage or inadequate pelvic lymph node dissection (harvested lymph nodes number of less than four). Toxicity from treatment was recorded when genitourinary or gastrointestinal (GI) events occurred. Results: The median follow-up was 43 months (8 to 103 months). The independent predictors for poor bRFS were time to PSA failure less than or equal to 1 year, PSA at salvage greater than 1 ng/mL, PSA doubling time less than 6 months, and PBRT alone group. The risk of BCF after salvage RT was significantly higher in PBRT alone group in comparison to that of WPRT with hormone group (hazard ratio [HR], 3.9; 95% CI, 1.8-8.3, p &lt;0.001), but the outcomes of PBRT with hormone was not statistically different from that of WPRT with hormone (p = 0.67). The advantage of WPRT and hormone over PBRT alone was only observed in the high-risk patients (HR, 5.7; 95% CI, 1.8-17.7, p = 0.003), and not in other patients (HR, 3.2; 95% CI, 0.7-14.9. p = 0.14). Patient treated with WPRT had more greater than or equal to grade 2 late GI toxicity than those having PBRT (17% vs. 5%, p= 0.01). Conclusions: Patients with postoperative high risk features could benefit from WPRT and hormone therapy for postoperative BCF. The additional toxicity by WPRT and long-term outcomes warrant further investigations.
The Personalized RNA Interference to Enhance the Delivery of Individualized Cytotoxic and Targeted Therapeutics (PREDICT) approach to biomarker discovery in renal cell carcinoma.
Authors: M. Gerlinger, L. Albiges
Journal: Journal of Clinical Oncology (2011)

TPS179 Background: Inhibitors of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR) have revolutionised the treatment of metastatic renal cell carcinoma (mRCC) but predictive biomarkers have not been identified. The PREDICT Consortium has opened 2 biomarker discovery trials of everolimus (E-PREDICT) and sunitinib (S-PREDICT) in untreated mRCC to acquire paired pre-treatment biopsies and on-treatment nephrectomy specimens for molecular analyses and integration with clinical efficacy data. Methods: Anglo-French multicentre single arm phase II trials of everolimus (E) or sunitinib (S) administered peri-nephrectomy (NE) in patients with untreated mRCC are open to recruitment. Interventions: sunitinib and everolimus are given for 12 and 6weeks, respectively, prior to NE and resumed afterwards until disease progression at metastatic sites. Sample size: 60 pts in both biomarker discovery and validation cohorts per trial will allow the identification and validation of several potential predictive biomarkers per drug with an expected AUC of >0.8 in a ROC analysis while controlling the false positive rate < 5%. The primary clinical endpoint is the safety of peri-NE E/S. Secondary endpoints include efficacy and biomarker measurements. Fresh tissue is collected in a quality-controlled setting by core biopsy of primary tumours before treatment and from NE specimens. Genes regulating drug resistance will be identified in ex vivo RCC cultures from trial patients by a novel personalized functional genomics screening approach. This functional data will be integrated with genome wide molecular analyses of pre- and on-treatment samples, survival and functional imaging data in order to identify clinically relevant mechanisms of drug resistance and predictive biomarkers. Sample size estimations, standardized tissue collection and processing protocols as well as planned genomic analyses of and functional genomic screens will be further discussed.
Quantifying physician performance using peer review during prospective contouring rounds.
Authors: Brett Wayne Cox, Henry Chou, Ajay Kapur, Gina M. Goode, Jeffrey Antone, Anurag Sharma, Louis Potters
Journal: Journal of Clinical Oncology (2014)

125 Background: This study presents the results of a physician evaluation system (PES) associated with a novel prospective contouring rounds (CR). Traditional chart rounds in radiation therapy (RT) occur after treatment planning and initiation of therapy. In CR, peer review occurs at a more logical process-point, once the contours and written directive (WD) are completed, but before initiation of treatment planning. We previously reported that CR improved quality of care, with the percentage of timely, errorless cases increasing over time. Methods: Starting 9/12, all patients undergoing RT at a high-volume academic center were reviewed in a daily prospective CR attended by physicians, medical physicists, and therapists. The clinical suitability for RT, contours, prescription, and remainder of the WD were prospectively peer reviewed. PES was implemented in 9/13, with each case receiving a grade (A = no deficiencies, B = minor modifications of PTV,OARs, WD, or a prescription/WD mismatch, and C = incomplete contours, significant contour modifications, prescription changes, or laterality modifications). A's were cleared for planning. B's were cleared for planning once remediated. C's were re-presented at CR upon remediation. Information was pooled to determine physician performance by assigning a grade point average. Results: 1,260 cases from 10 physicians have been reviewed using the PES. 25% of cases (318 patients) required modifications before treatment planning commenced. The breakdown of grades was 70% A’s, 18% B’s and 12% C’s. The average number of cases reviewed per day was 7. The median number of weekdays between contour completion and CR review was 0.8 days. The median contour grade point average was 3.6 (3.3 – 3.9). Conclusions: Peer review during a prospective CR can be used to develop physician performance metrics. 25% of all cases required modifications before starting treatment planning, and 12% of cases required significant remediation. Using the PES, several metrics can be combined to transparently quantify general physician performance. We intend to develop this PES to improve physician performance, optimize continuing medical education efforts, and integrate its use in PQIs for MOC.