tbuckley/cabot-search huggingface dataset:
Associations between patient (pt) colorectal cancer (CRC) tumor KRAS and BRAF mutation (mut) status and overall survival (OS).
Authors: Hesham M. Hassabo, Ibrahim Halil Sahin, Syed Mohammad Ali Kazmi, Salwan S. Al Mutar, Diogo Bugano Diniz Gomes, Tunghi May Pini, Eduardo Vilar Sanchez, Arvind Dasari, Scott Kopetz, Michael J. Overman, Cathy Eng, Bryan K Kee, Jean-Nicolas Vauthey, Manal Hassan, Chris R. Garrett
Journal: Journal of Clinical Oncology (2014)

473 Background: Evolving information is emerging regarding patient tumor molecular data and associations with patient clinical characteristics and survival outcomes; we sought to evaluate pt clinical data with CRC tumor mut status. Methods: Since January 2008 tumor pts with stage IV CRC (principally primary tumors) were analyzed for KRAS (codon 12, 13, and 61) mut status as standard-of-care. A subset of pts tumors underwent BRAF and KRAS codon 164 mut testing. Results: 1,891 pts with CRC whose tumors underwent molecular mut analysis were identified from the clinical record. There was no statistically significant difference in pt overall survival from time of diagnosis for stages I/II (data not shown) and III; for stage IV pts there was an inferior OS associated with BRAF mut tumors (see Table). Tumor BRAF mut was significantly detected among ever smokers (10.2%) as compared to never smokers (5.4%), p &lt; 0.001; meanwhile, tumor KRAS mut and wild type distribution were similar between ever smokers and never smokers. KRAS mut was significantly observed in CRC patients with distant lymph node, hepatic and lung metastasis, p &lt; 0.001. Type 2 diabetes, intake of metformin or ACE inhibitors, were not significantly correlated with tumor KRAS or BRAF mut status. Conclusions: Pts with stage IV CRC BRAF mut tumors have a higher likelihood of prior or current smoking history in addition to having an adverse survival prognosis; pts with stage IV KRAS mut tumors have an increased association with distant lymph node, hepatic, and lung metastases as compared to KRAS wild type and BRAF mut tumors. Studies are ongoing to determine how tumor molecular characteristics may help to predict clinical outcomes and provide a useful to guide pt care. [Table: see text]
Neurovascular bundle-sparing radiotherapy for prostate cancer using MRI-CT registration: A dosimetric feasibility study.
Authors: Richard John Cassidy, Xiaofeng Yang, Tian Liu, Sherif Nour, Ashesh B. Jani
Journal: Journal of Clinical Oncology (2016)

128 Background: Sexual dysfunction after radiotherapy for prostate cancer remains an important late adverse toxicity. The neurovascular bundles (NVB) that lie postero-laterally to the prostate are typically spared during prostatectomy, but in traditional radiotherapy planning they are not contoured as an organ-at-risk with dose constraints. Our goal was to determine the feasibility in sparing the NVB while still delivering adequate dose to the prostate. Methods: Twelve consecutive patients with intermediate- or high-risk prostate cancer (with no gross disease within 2mm of either NVB) who were treated with external beam radiotherapy, with the same primary PTV margins, to a dose of 79.2 Gy were evaluated. Pelvic MRI and simulation CT scans were registered using dedicated software to allow for bilateral NVB target delineation on T2-weighted MRI. A volumetric modulated arc therapy (VMAT) plan was generated using the NVB bilaterally with 2mm margin as an organ to spare (with goal of reducing V70Gy by 30%) and compared to the patient’s delivered plan. Dose-volume histogram (DVH) endpoints for NVB, rectum, bladder, and PTV79.2 were compared between the two plans using a 2-tailed paired t-test. Results: The V70 for the NVB was significantly lower on the NVB sparing plan (p &lt;0.01), while rectum and bladder endpoints were similar. Target V100% was lower (but still &gt; 95%), and V105 was higher for the NVB Sparing plans (p &lt;0.01). The table summarizes the DVH comparisons between the two plans. Conclusions: “NVB-sparing” radiotherapy is dosimetrically feasible using VMAT technology; target coverage is acceptable without increased dose to other normal structures, but with higher target dose inhomogeneity. The clinical impact of “NVH-sparing” radiotherapy is currently under study at our institution. [Table: see text]
Phase II study and biomarker analysis of cetuximab in combination with oxaliplatin, 5-fluorouracil, leucovorin as first-line treatment in patients with recurrent or metastatic gastric cancer
Authors: S. Han, S. R. Park, K. Lee, H. Song, M. A. Kim, D. Oh, S. Im, W. Kim, Y. Bang, T. Kim
Journal: Journal of Clinical Oncology (2008)

4549 Background: This multicenter study was conducted with Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in patients with recurrent or metastatic gastric cancer and the association with potential biomarkers. Methods: Previously untreated recurrent or metastatic gastric cancer patients received cetuximab 400 mg/m2 at first week and then 250 mg/m2 weekly until disease progression. Oxaliplatin (100 mg/m2) and leucovorin (100 mg/m2) was administered as a 2-hour infusion followed by a 46-hour continuous infusion of 5-FU (2,400 mg/m2) every 2 weeks for a maximum of 12 cycles. Response was evaluated 6-weekly during cetuximab/mFOLFOX6 treatment and 8-weekly afterwards. Biomarker analyses were performed using immunohistochemistry (EGFR, HER2, TS, TP, ERCC1), FISH (EGFR, HER2), direct sequencing (K-ras), PCR-RFLP, and ELISA. Results: 40 patients (pts) were enrolled from Dec 2006 to Jun 2007: male/female 30/10 pts, median age 55 (range 33–74), ECOG PS 0/1/2: 7/29/4 pts, recurrent/initially metastatic 5/35 pts. Among 38 evaluable pts, partial response was seen in 19 pts (response rate 50.0 %; 95% CI 34.1 - 65.9) and disease control rate (PR+SD) was 92.1 % (95% CI 83.5 - 100.0). Median time-to-progression (TTP) was 5.5 months (mo) (95% CI 4.8 - 6.2). Median overall survival (OS) was 9.9 mo. Toxicity was assessable in 39 pts. Grade 3/4 toxicities include neutropenia 4/3 pts, thrombocytopenia 0/1 pt, stomatitis 3/0 pts, diarrhea 4/0 pts, skin rash 3/0 pts. There was 1 treatment-related mortality (febrile neutropenia). In the immunohistochemical analysis, low TP expression was associated with longer TTP (p = 0.013) and OS (p = 0.031). Pts with HER2 2+/3+ tended to have longer TTP (p = 0.079) and pts with low TS (p = 0.098) and low ERCC1 (p = 0.070) longer OS. No patient exhibited EGFR amplification or K-ras mutation. HER2 amplification was seen in 5 pts, but was not associated with outcomes. Other biomarker analyses are currently underway and will be presented at the meeting. Conclusions: Cetuximab/mFOLFOX6 is an active first-line treatment in patients with advanced gastric cancer. No significant financial relationships to disclose.
Brain metastasis from renal cell carcinoma: Are we missing our chance to treat?
Authors: Michael Hanzly
Journal: Journal of Clinical Oncology (2014)

485 Background: Brain metastasis from renal cell carcinoma (RCC) occurs approximately 8% of patients with metastatic RCC. The guidelines from the NCCN, EAU, and AUA recommendcerebral imaging only in patients who have symptomatology. The purpose of our study was to review the presenting symptomatology that led to their diagnosis of brain metastases followed by their overall treatment and survival. Methods: Our IRB-approved prospectively-maintained kidney cancer data base was reviewed between from 1995 to 2012. Brain metastases from a primary RCC was identified in 52 patients. Patient demographics including family and social history, primary treatment for RCC, elapsed time between primary diagnosis and brain metastasis, associated symptomatology, treatment of metastatic site and overall survival following diagnosis of brain metastasis were examined. Results: Primary RCC was diagnosed in 986 patients between 1995 and 2012. Brain metastases were identified in 52 patients, 79% were male and 100% Caucasian, 87% had no family history of renal malignancy. Primary treatment for RCC included 75% radical nephrectomy, 10% observation, 7.6% cytoreductive nephrectomy, 5.4% sunitinib, 2% interleukin-2 treatment. Central nervous system (CNS) symptoms were absent in 37% of patients diagnosed with brain metastases, while 73% presented with symptoms. The average number of metastases was 1.78 per patient in the asymptomatic group, and 2.7 metastases in patients with CNS symptoms (p=.18). Elapsed time from primary RCC treatment to diagnosis of brain metastases was an average of 730 days in the asymptomatic group and 1170 days for the symptomatic group (p=0.02). The symptomatic group has overall survival (OS) at one year of 81% and 69% at three years, while the asymptomatic group had an OS of 81% at one year and 31% at 3 years. Pulmonary involvement existed in 75% of both cohorts of patients (p=0.003). Conclusions: Our findings suggest that patients without CNS symptoms with brain metastases had a worse overall survival. The urologic guidelines recommending CNS imaging only in patients with symptoms may be missing a subset of the metastatic RCC population who could potentially benefit from early intervention, thus prolonging overall survival.
The association between sociodemographic parameters and the use of complementary interventions in patients with cancer in Turkey: A Turkish Oncology Group study.
Authors: N. S. Turhal, S. Kilickap, S. Yalcin, C. Sezgin, D. Yamac, H. Akbulut, O. Ozyilkan, F. Ozdemir, D. Cabuk, A. Sevinc
Journal: Journal of Clinical Oncology (2011)

e19598 Background: The extent of the use of complementary interventions has not yet been assessed in a multicentre study in the entire country. Methods: A questionnaire consisting of 32 questions was completed by 872 patients in ten different medical institutions, which included over 90% of the oncological care given in Turkey, were represented. To allay patients’ concerns that their answers could influence their treatment, the questionnaire was given to each patient by support people and not by the attending physician. Results: For the sample of 872 patients, 44% were male and 55% were female. The median age of the patients was 55 ± 13 (range 16-89). The average age of the male patients was significantly greater than that of females (57 versus 53; p< 0.001). Of all patients, 165 (18.9%) used some form of complementary interventions during their illnesses.We found no evidence that the use of complementary treatments was associated with any of the remaining demographic variables. Frequency of patients who used complementary interventions varied significantly (p<0.002) among medical institutions. The most frequent cancers in the sample were gastrointestinal system cancers (29%), breast cancer (27%), and lung cancer (19%). However, complementary interventions were used most frequently by patients with prostate cancer (33%), head and neck cancer (27%), and lung cancer (22%). The patients who were least likely to use complementary interventions were the patients with soft tissue tumors. The most frequently used method (85%) was a mixture of various herbs. Other common methods included praying (10%) and vitamins (8%). Forty-one percent of the patients who used complementary interventions were using some sort of it during the time that they filled out the questionnaire. Sources of information regarding complementary interventions included relatives (37%), television (26%), other patients with cancer (22%), and the internet (21%). Fifty-five percent of patients thought that they benefited from these methods. Conclusions: Approximately 20% of cancer patients in Turkey used complementary interventions and this frequency was lower than expected.
A comparison of rates and predictors of hospital readmission: Outpatient versus inpatient mastectomy for breast cancer.
Authors: Lori Uyeno, Leanne Streja, John H. Yim, Steven L. Chen, Laura Kruper
Journal: Journal of Clinical Oncology (2013)

116 Background: The odds of readmission have been reported to be slightly higher with outpatient (OP) compared to inpatient (IP) mastectomy, although overall rates are low. While OP mastectomy procedures have become more common, predictors of readmission and current rates are unknown. Methods: Observational study of women 18+ years who underwent mastectomy in California from 2005-2009 from the Healthcare Cost and Utilization Project (HCUP) linked state database. Associations of readmission and post-mastectomy complications with length of stay (LOS) were assessed using Jonkheere – Terpstra test for trend. Multivariate logistic regression was used to test the association of LOS with readmission to hospital within 30 days, adjusting for patient, clinical, and hospital factors. Results: Readmission rates for OP compared to IP mastectomy was 3.3 % vs. 5.6% (p&lt;0.0001). OP mastectomy had the highest hematoma/seroma and chemotherapy related anemia/ neutropenia readmissions (19% p=0.0112; 2.9% p=0.0009). Readmits for cardiopulmonary events were higher for the longest LOS. Multivariate analysis showed increased readmission rates by LOS, race, payer, comorbidities (all p-values &lt;0.0001). Odds of readmission were higher with increasing LOS vs. OP (1d OR 1.13 95% CI 0.99-1.3; 2d OR 1.6 95%CI 1.4-1.8; ≥3d OR 3.0 95%CI 2.6-3.4). Increased odds of readmission was associated with African-Americans (OR 1.5 95%CI 1.2-1.9) and Whites (OR 1.4 95%CI 1.2-1.7) vs. Asians. Revisit rates were higher with Medicare (OR 1.7 95%CI 1.4-1.9) and Medicaid (OR 1.6 95%CI 1.3-1.8) compared to private insurance. The highest readmission rates were ≥ 3 comorbidities (OR 2.7 95%CI 2.2-3.2). Conclusions: In California, readmission rates increase with increasing LOS. Risks of readmission following IP mastectomy are higher compared to OP. Low readmission rates suggest appropriate selection of patients for OP mastectomy. However, subsets of patients are at higher risk of readmission. Additional studies of patients with extended LOS; racial disparities in access to services; and evaluation of payer policies are needed to improve care and decrease hospital readmissions.
A novel and robust technique for determining lymph node status in colorectal cancer.
Authors: John Hogan, Michael O Callaghan, Conor Judge, Cormac O Connor, A Aziz, John Burke, Cormac Dunne, Matthew Kalady, Stewart Walsh, Calven Coffey
Journal: Journal of Clinical Oncology (2014)

483 Background: Currently, techniques that determine lymph node positivity (prior to resection) have poor sensitivity and specificity. The ability to determine lymph node status, based on preoperative biopsies, would greatly assist in planning treatment in colorectal cancer. This is particularly relevant in polyp-detected cancers. This study aims to harness the potential of public gene expression repositories, to develop gene expression profiles that could accurately determine nodal status in colorectal cancer. Methods: Public gene expression repositories were screened for experiments comparing metastatic and non-metastatic colorectal cancer. A customized graphic user interface was developed to extract genes dysregulated across the majority of identified studies (i.e., consensus profiles or “CP”). The utility of CP was tested by determining if classifiers could be derived that determined nodal positivity or negativity. CP-derived classifiers were tested on separate Affymetrix and Illumina–based experiments and collated outputs compiled in summary-receiver operator curve characteristic format. The association between classification and oncologic outcome was determined using an additional, independent data set. Results: Four consensus profiles were generated from which classifiers were derived that accurately determined node positive and negative status (pooled AUC were 0.79 ± 0.04 and 0.8 ± 0.03 for nodal positivity and negativity respectively). Overall AUC ranged from 0.73 to 0.86 demonstrating high accuracy across consensus profile type, classification technique and array platform used. As CP enabled classification of nodal status, survival outcomes could be compared for those predicted node negative or positive. Patterns of disease-free and overall survival were identical to those observed for standard histopathologic nodal status. Genes contained within consensus profiles were strongly linked to the metastatic process and included FYN, WNT5A, COL8A1 and BMP. Conclusions: Microarray expression data available in public gene expression repositories can be harnessed to generate consensus profiles. The latter are a source of classifiers that have prognostic and predictive properties.
An Innovative Humanized Mouse Model of Multiple Myeloma (MM) for Studying MM in Its Natural Environment Using Multi-Color Light Sheet Fluorescence Microscopy (LSFM)
Authors: Sabrina Kraus, Martin Chopra, Christian Brede, Simone S Riedel, Mike Friedrich, Jürgen Pinnecker, Anja Mottok, Christian Langer, Silke Brüderlein, Peter Möller, Jeanette B Baker, Hermann Einsele, Katrin G Heinze, Andreas Beilhack
Journal: Blood (2012)
Whole-genome expression profiling of brain metastases from melanoma (BrMM) provides preliminary insights into its biology and mechanisms of development.
Authors: M. T. Krauze, R. H. Hamilton, S. Bortoluzzi, S. C. Buch, M. Romkes, A. H. Mintz, D. Kondziolka, J. M. Kirkwood, S. J. Moschos
Journal: Journal of Clinical Oncology (2011)

8515 Background: BrMM accounts for a major fraction of the mortality from melanoma and little is known about the biology of BrMM or its association with extracranial metastases (EcMM) and primary melanoma (PrM). This would provide insights about BrMM pathogenesis and lead to better prognostic and therapeutic targets. We hypothesize that BrMM differ from EcMM and PrMs in gene expression levels. These signatures will provide insight to the pathogenesis and lead to better prognostic and therapeutic targets. Methods: We have performed whole genome expression profiling (DASL assay, Illumina; 28,688 genes) of formalin-fixed paraffin-embedded (FFPE) tissue blocks corresponding to paired specimens (BrMM and EcMM) from patients (pts) undergoing craniotomy at UPCI. We performed class comparison analysis using paired t tests to identify differentially expressed genes. Results are presented as the ratio of the geometric mean of EcMM/BrMM. Results: Paired analysis of FFPE tumor blocks from 12 pts has been accomplished (n=24). 187 genes were differentially (p<0.05) expressed between BrMM and EcMM. The table shows gene categories of most significantly dysregulated genes. We confirmed that upregulation of GFAP in BrMM derives from melanoma cells and not normal brain using immunohistochemical analysis of GFAP protein in BrMM, EcMM, and PrM from the same pt. Conclusions: The upregulation of neuronal differentiation genes in BrMM underscores the potential of melanoma cells to transdifferentiate (plasticity) although the clinical significance is currently unknown. The upregulation of immune tolerance and ECM remodeling genes in EcMM challenges the prevailing notion that BrMM is the last step in the metastatic cascade. Profiling PrM is underway. Function EcMM/BrMM Extracellular matrix (ECM) remodeling Cartilage intermediate protein 6.2 Matrix metallopeptidase 9 5.3 Cartilage oligomeric matrix protein 4.9 Microfibrillar-associated protein 5 3.2 Neural differentiation/function Gliomedin 0.15 Glutamate receptor, metabotropic 3 0.23 Glial fibriallary acidic protein (GFAP) 0.26 Immune tolerance Chemokine ligand 19 3.6 Chemokine ligand 21 3.6 CTLA4 2.4
Molecular analysis of endometrial pathogenesis in Lynch syndrome.
Authors: M. Huang, B. Djordjevic, D. Urbauer, S. N. Westin, C. C. Sun, J. K. Burzawa, L. Meyer, D. C. Bodurka, R. Broaddus, K. H. Lu
Journal: Journal of Clinical Oncology (2011)

5095 Background: Women with Lynch Syndrome (LS) have a 40-60% predicted lifetime risk of developing endometrial cancer (EC). We hypothesize that in LS-associated EC, normal endometrium accumulates molecular changes in a step-wise fashion similar to sporadic EC. The objective of this study was to investigate precursor lesions and identify molecular changes contributing to endometrial carcinogenesis in LS-associated EC. Methods: Women with a confirmed mismatch repair gene mutation for LS undergoing a prophylactic or therapeutic hysterectomy were eligible. Case controls were matched 2:1 for EC and hyperplasia based preferentially on age and histology. Molecular analysis of PIK3CA, KRAS, AKT, and CTNNB1 was performed using Sequenom MassArray system. PTEN expression was assessed by immunohistochemistry. Statistical analysis was performed using Fisher’s exact test. Results: There were 67 patients with LS (30 normal endometrium, 8 hyperplasia, 39 EC) and 84 patients (10 normal endometrium, 16 hyperplasia, 58 EC) in the case matched control group. Concurrent complex atypical hyperplasia (CAH) was found in EC in 11 (39.3%) and 21 (46.6%) of LS and sporadic cases respectively. Loss of PTEN expression did not differ between sporadic (69%) and LS EC (86.2%) (p=0.117). However, sporadic CAH demonstrated 68.8% PTEN loss compared to only 12.5% in LS CAH (p=0.056). There was no difference in KRAS frequency in sporadic EC (10.3%) compared to LS EC (3.4%) (p=0.416). PIK3CA mutations occurred more frequently in sporadic EC (39.7%) compared to LS EC (13.8%) (p=0.015). Sporadic EC (37.9%) had significantly more CTNNB1 mutations than LS EC (6.9%) (p= 0.002). There was no relationship between PIK3CA, KRAS, AKT and CTNNB1 mutation and loss of PTEN expression. Conclusions: Similar to sporadic EC, hyperplasia is part of the pre-invasive spectrum of disease in LS associated EC. While PTEN loss was common in both LS and sporadic EC, PIK3CA and CTNNB1 mutations were more frequent in sporadic EC than LS EC. Our results indicate that loss of PTEN expression is an early event in sporadic EC and that other common mutations in sporadic EC may have a lesser role in LS associated EC development.