tbuckley/cabot-search huggingface dataset:
Genomic profile associated with clinical outcome of EGFR-expressing metastatic colorectal cancer patients treated with epidermal growth factor receptor (EGFR) inhibitor cetuximab
Authors: W. Zhang, D. Vallböhmer, D. Yang, J. Yun, O. A. Press, M. Gordon, K. Rhodes, A. Sherrod, S. Iqbal, H.-J. Lenz
Journal: Journal of Clinical Oncology (2005)

3557 Background: Cetuximab is a chimeric anti-EGFR monoclonal antibody with efficacy against EGFR-expressing metastatic colorectal cancer and it was recently approved for use to treat irinotecan refractory metastatic colorectal cancer. Our group has reported association between germline polymorphisms in genes involved in EGFR signaling pathway and overall survival of metastatic colorectal cancer patients treated with Cetuximab at ASCO 2004. This year, we updated this genomic profile and moreover, we studied the correlation between these gene polymorphisms and gene expression levels. Methods: we tested gene polymorphisms and gene expression levels of following important genes involved in EGFR signaling pathway (EGFR,VEGF,COX-2,CyclinD1,IL-8, EGF and E-cadherin) using PCR-RFLP method in genomic DNA extracted from peripheral blood and quantitative realtime RT-PCR in microdissected paraffin-embedded tumor tissue from 39 EGFR-expressing metastatic colorectal cancer patients enrolled in a phase II single agent Cetuximab treatment clinical trial(IMCL-0144). Results: We found a trend of association between EGF A61G polymorphism and overall survival of patients treated with Cetuximab. With median follow-up 7.1 months (95%C.I 2.5, 21.6) and median survival time 5.5 months (95%C.I 2.7, 8.7), Patients with AA homozygous genotype survived a median time of 15.0 months (95%C.I 2.3, 15.9) compared with those have homozygous GG genotype 2.3 months (95%C.I 1.8, 7.3) or heterozygous AG genotype 5.7 months (95%C.I 2.7, 10.7), respectively (p=0.07, logrank test). Also, there is a trend of association between CylinD1 A870G polymorphism and intratumor gene expression levels (p=0.12, Kruskal-Wallis test), no association found between other gene polymorphism and gene expression levels. Conclusions: These data suggest that genomic profile of genes in the EGFR signaling pathway may be potential molecular markers for clinical outcome of the EGFR-expressing refractory metastatic colorectal caner patients treated with single agent EGFR inhibitor Cetuximab. Prospective studies are needed to confirm these preliminary findings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron, Genentech, Response Genetics Lilly Oncology, Pfizer, Roche, Sanofi National Cancer Institute, National Institutes of Health
Pretreatment [18F] FDG-PET texture analysis to predict local response of pancreatic cancer to radiotherapy.
Authors: Richard Tuli, Benedick Fraass, Wensha Yang, Howard Mark Sandler, Andrew Hendifar, Nicholas N. Nissen, Yong Yue
Journal: Journal of Clinical Oncology (2014)

375 Background: Accurate assessment of radiographic response following radiotherapy (RT) for pancreatic adenocarcinoma is challenging. Morphologic and textural features of FDG-PET have been shown to correlate with pathologic response and clinical outcomes in other solid tumors (PMID 23204495). The goal of this study was to develop a predictive algorithm derived from textural features of PET scans to predict response to RT. Methods: With IRB approval, we reviewed 10 patients with locally advanced pancreatic cancer treated with stereotactic body radiation therapy (25-30 Gy in 5 daily fractions). 18FDG-PET/CT scans were obtained 2 weeks pre-RT and 6 weeks post-RT. Pre-RT PET/CT images were deformably registered to the RT planning CT. Tumor volumes of interest were divided into (4.8mm)^3 subvolumes and characterized by mean SUV uptake, RT dose and comprehensive texture analysis. These pre-RT variables were correlated to post-RT mean SUV to identify potential predictors of treatment response. Response prediction was modeled by logistic regression with the Lasso algorithm and validated by 10-fold cross-validation. Model performance was assessed using cross-validated area under the receiver operating characteristic curves (AUC). Results: Mean uptake, RT dose and 6 texture features (energy, correlation, variance, sum mean, cluster tendency, and inverse variance) on pre-RT PET scans were significant in predicting treatment response (AUC 0.85). Within this model, each of the above noted variables was predictive of post-RT response (p&lt;.05). Conclusions: Subvolume-based metabolic and texture features of pre-treatment PET scans were predictive of response following RT. Studies are ongoing to further correlate these variables to RECIST and pathologic response. This should serve as a useful model to help direct response-driven adaptive radiotherapy in patients with locally advanced pancreatic cancer.
Quality of life implications of osteonecrosis of the jaw in cancer patients: a pilot study
Authors: R. A. Miksad, S. Woo, T. Dodson, N. S. Treister, G. Maytal, M. August, O. Akinyemi, M. M. Bihrle, J. S. Swan
Journal: Journal of Clinical Oncology (2008)

17557 Background: Presenting as exposed, necrotic bone, osteonecrosis of the jaw (ONJ) is associated with intravenous (IV) bisphosphonate use in cancer patients. Because these patients usually have incurable cancers, side effects that decrease health related quality of life (HRQoL) need to be understood. The overall aim of the study is to estimate the QoL impact of ONJ in order to inform individual and societal bisphosphonate treatment decisions; the aim of this pilot study was to develop and test the feasibility of the survey instruments, assess the level of emotional discomfort caused by the survey and provide preliminary QoL estimates. Methods: A phone survey was developed in collaboration with oncology, oral medicine, oral surgery, psychiatry and QoL experts. Subjects were randomly identified from a cohort of 80 cancer patients with ONJ. A chart review determined eligibility. Oral health-specific QoL before and after ONJ was determined with the Oral Health Impact Profile (OHIP), a validated psychometric instrument. Four standardized health states for cancer in the bone and ONJ were developed and preference values (utilities) for each state were obtained using the Visual Analogue Scale (VAS), the EQ5D and time- tradeoff (TTO) questions. Emotional discomfort during and after the survey was evaluated. Results: With a response rate of 100%, the pilot study included 5 subjects. Two subjects reported “a little” emotional discomfort during the survey (2 on a 5 point Likert scale) but none were upset afterwards. The mean OHIP score was 1.6 pre-ONJ and 7.2 post-ONJ (0–28 scale). The largest change occurred for the pain domain (mean increase =1.2). The only domain not affected was overall function. Subjects reporting more ONJ symptoms had larger OHIP score changes. The utility value decreased when cancer in bone alone was compared to cancer in the bone with Stage 3 ONJ: 0.76 to 0.42 (VAS), 0.88 to 0.49 (EQ5D) and 0.86 to 0.56 (TTO). Rank order was appropriate and consistent across instruments. Conclusions: Preliminary results suggest study design was feasible and instrument results were internally consistent. Both oral-health specific and global HRQoL instruments capture QoL changes associated with ONJ. There was minimal subject distress. No significant financial relationships to disclose.
Febrile neutropenia rates during docetaxel and cyclophosphamide (TC) adjuvant therapy in early breast cancer (EBC).
Authors: D. Kotasek
Journal: Journal of Clinical Oncology (2011)

1101 Background: Numerous options exist for adjuvant chemotherapy in EBC. Docetaxel cyclophosphamide (TC) is increasingly used because of its superiority over doxorubicin and cyclophosphamide (AC) (Jones et al 2009), and the lack of anthracycline induced cardiac injury. Myelosuppression and febrile neutropenia are frequent adverse events (AE) of TC. Jones reported that in the phase III trial FN occurred in 5% of all patients and in 8% of those over 65. There was no requirement for use of prophylactic growth factors or antibiotics in the trial. Subsequent publications have reported rates of FN ranging from 25-50% (Chan 2010, Vandenberg 2010, Soong 2009). Methods: We investigated the frequency of FN in consecutive EBC patients treated with TC in a community practice setting of predominantly high socio-economic class, fit patients, and examined the effect of primary prophylaxis with pegfilgrastim. We anticipated low rates of FN. Results: 74 EBC patients (median age 58 yrs, range 35-84 yrs) were treated between 1/2008 and 8/2010 with TC (T 75 mg/m2, C 600 mg/m2) given at 21 d cycles for 4-6 cycles. 53 patients (median 57.5 yrs, range 35-84) did not receive primary pegfilgrastim prophylaxis, while 21 patients (median 59 yrs, range 42-79) received primary prophylaxis. Prophylactic antibiotics were not used. 59 patients received 4 cycles of TC, 14 patients received 6 cycles, 1 had a single cycle. Most patients who developed FN (11/16) received secondary pegfilgrastim prophylaxis. The overall incidence of FN was 21.6% (16/74 patients) 0% (0/21) in those given primary prophylaxis and 30% (16/53) in those given no prophylaxis. Of the 13 patients aged >65yrs 2 (15%) developed FN. The rate of FN with secondary prophylaxis was 18% (2/11). Major differences exist in rates of hospitalization. Conclusions: We were surprised to see such high rates of FN in a medically fit and generally well population. Our results are consistent with others, and significantly in excess of the original study. We recommend that all patients receiving TC therapy in EBC receive primary pegfilgrastim prophylaxis or prophylactic antibiotics.
Molecular prognostic factors of irinotecan efficacy
Authors: D. Y. Yang, D. Vallböhmer, K. E. Rhodes, W. Zhang, J. Yun, O. A. Press, M. Gordon, S. Iqbal, K. D. Danenberg, H.-J. Lenz
Journal: Journal of Clinical Oncology (2005)

3621 Background: The most commonly used chemotherapeutic drugs in the treatment of metastatic colorectal cancer (CRC) are 5-fluorouracil (5-FU), oxaliplatin and irinotecan (CPT-11). There are no reliable prognostic factors to predict clinical outcome of CPT-11 treatment. We investigated whether mRNA levels of factors involved in the 5-FU metabolism (TS, DPD), in the CPT-11 metabolism (MDR1, Topoisomerase I), in angiogenesis (Cox-2, EGFR, IL-8, VEGF) and in DNA-repair/drug detoxification (ERCC1, GSTP1) are associated with the clinical outcome of patients with CRC treated with first-line 5-FU/Leucovorin/CPT-11. Methods: Thirty-three patients with metastatic CRC treated with first-line CPT-11 at USC between 2000 and 2003 were included in the study. Intratumoral gene expression levels were assessed from paraffin-embedded tissue samples using laser capture microdissection and quantitative Real-time PCR. Results: There were 16 women and 17 men (median age 53; range 40–75) with a median survival time of 27.9 months, median time to tumor progression of 9.9 months and median follow-up of 24.8 months. Complete response was observed in 1 (3%) patient, partial response in 12 (36%), stable disease in 13 (40%) and progressive disease in 6 (18%) patients (response was inevaluable for 1 patient). High intratumoral mRNA levels of EGFR, ERCC1, GSPTP1 and MDR1 were each significantly associated with response to CPT-11 based chemotherapy (p≤0.05). No significant association was found between mRNA levels and time to tumor progression. The mRNA levels of EGFR had a statistically significant correlation with ERCC1, GSTP1, MDR1 and VEGF (Spearman correlation coefficients ≥0.4; p<0.05). Conclusions: This retrospective study, with a small number of patients, suggests that gene expression levels of EGFR, ERCC1, GSPTP1 and MDR1 may be useful to predict the clinical outcome of patients with metastatic CRC with first-line CPT-11 based chemotherapy. It is consistent with recent studies suggesting an increased CPT-11 sensitivity mediated by higher EGFR expression and supports the previously reported relationship between EGFR and ERCC1/GSTP1. The role of MDR1 remains unknown. Our data are hypothesis generating and should be validated in larger and prospective clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics Chiron, Response Genetics, Genentech Response Genetics Roche, Pfizer, Lilly Oncology, Sanofi NCI, NIH
Monitoring of BCR-ABL Transcirpt Levels after Discontinuation of Imatinib Therapy in Chronic Myelogenous Leukemia Patients Achieving Complete Cytogenetic Response.
Authors: Yoo-Jin Kim, Dong-Wook Kim, Seok Lee, Ki-Seong Eom, Chang-Ki Min, Hee-Je Kim, Jong-Wook Lee, Woo-Sung Min, Chun-choo Kim
Journal: Blood (2004)
Using real time locating systems (RTLS) to redesign room allocation in an ambulatory cancer care setting.
Authors: Beth Overmoyer, Sarah Kadish, Courtney Haskett, Kendall Sanderson, Jim Benneyan, Christine Reilly, Lillian Vitale Pedulla, Linda Brown, Kristen Camuso, Craig A. Bunnell
Journal: Journal of Clinical Oncology (2014)

157 Background: Growing clinics need innovative ways to maximize capacity to ensure efficiency, a core element of quality care. Providers at the Dana-Farber Cancer Institute (DFCI) are assigned specific exam rooms for each clinic day. Despite room utilization below 50%, providers reported feeling constrained, and patients waited an average of 15 minutes to room. Furthermore, in February 2014, DFCI consolidated two facilities requiring that clinics absorb an immediate 10% increase in patient volume using available capacity. We sought to redesign the exam room allocation process by leveraging RTLS. Methods: Using computer simulation, we compared three options for allocating exam rooms. The simulation indicated a “pooled” room approach that did not designate rooms to individual providers would minimize patient wait time. A team was assembled to pilot the intervention in one clinic. An algorithm was developed to prioritize patients based on appointment time, arrival time, and provider availability. We utilized RTLS to automate the algorithm and indicate available exam rooms to coordinate transport of patients from the waiting area to exam rooms. Patient wait time was extracted from RTLS and compared between the baseline (provider-designated rooms) period and the post-intervention (pooled, undesignated rooms) period. Providers were asked post-intervention to provide feedback using a survey. Results: There was a significant decrease in the average wait to exam room despite a simultaneous increase in average appointment volume during the post-intervention period. Cumulative wait time gains averaged 3.3 hours daily. In addition, providers preferred the pooled rooming method over the designated rooming method. Conclusions: Allowing providers to utilize any available room has allowed this clinic to efficiently accommodate a larger number of appointments per day with an overall decrease in patient wait time. RTLS provided the real-time information necessary to succeed and drive improvement initiatives. [Table: see text]
Feasibility of plasma circulating free RNA (cfRNA) microarray profiling and gene-specific prognostic associations in metastatic urothelial carcinoma (mUC) patients receiving platinum-based chemotherapy.
Authors: Noah M. Hahn, Zhiping Wang, Yunlong Liu, Marietta L. Moore, Nagendra K Prasad
Journal: Journal of Clinical Oncology (2015)

333 Background: The current study was undertaken to determine the feasibility of detection and expression profiling of cfRNA in mUC patients treated with platinum-based chemotherapy. Methods: Plasma samples were identified from consented mUC subjects treated with platinum-based therapy at the IU Simon Cancer Center (IUSCC) from 12/2008 – 8/5/2010. The primary feasibility measure was the detection of cfRNA at any quantitative level. An IUSCC urologic cancer 48-gene array was designed. After cfRNA extraction and cDNA preparation, cDNA were amplified in a specific target amplification step using gene-specific primers for the 48 genes in the array. Gene expression analysis was performed on amplified cDNA using 96.96 format DELTAgene microfluidic Dynamic Array platform (Fluidigm). C T values were calculated for each gene after normalization against expression of internal control gene, GAPDH. To identify associations between individual gene expression and OS, a Cox proportional hazards regression analysis was performed. Results: Plasma samples and OS data were available from 15 pts. Patient demographics included: median age – 70.8, M/F – 14/1, Cisplatin/Carboplatin regimen – 9/6, lymph node/visceral mets – 13/7. Median PFS/OS were 8.7 and 23.0 months respectively. cfRNA was detectable in all 15 patients (100%). Median quantitative cfRNA concentration was 2.68 ng/ml (range 1.9 – 6.3). 96.96 Dynamic Array was performed in all patients. All 48 gene probes passed QC testing and produced C T values suitable for analysis. On univariate analysis, overall survival was significantly associated with presence of visceral metastases and plasma cfRNA expression of AKT1, AKT2, BRCA1, CCND1, HPRT1, HSD3B1, PARP1, and RPA3 (all p &lt; 0.05). Conclusions: Successful extraction of cfRNA suitable for microarray analysis from archived mUC patient plasma samples is feasible. Intriguing hypothesis generating associations between OS and cfRNA expression of genes mediating DNA repair, apoptosis, and cell-signaling pathways were observed. Demonstration of these findings in larger independent patient cohorts is warranted.
B-Cell Depletion and Prevention of Hemolysis in Allogeneic Peripheral Blood Stem Cell Transplantation with Minor ABO Incompatibility.
Authors: Emmanuelle Tavernier, Anne Thiebaut, Franck Nicolini, Quoc Hung Le, Xavier Thomas, Youcef Chelghoum, Daniela Revesz, Olivier Hecquet, Philippe Dubost, Jean-Paul Bourgeot, Mauricette Michallet
Journal: Blood (2004)
Qualitative study of patients’ and family caregivers’ (FC) perceptions and information preferences about hospice.
Authors: Areej El-Jawahri, Jennifer Adrienne Shin, Lara Traeger, Helen Knight, Kristina Mirabeau-Beale, Joel Fishbein, Harry VanDusen, Tanya Keenan, Vicki A. Jackson, Angelo E. Volandes, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2015)

50 Background: Despite the benefits of hospice for patients with advanced cancer and their FC, many patients are referred late or not at all. To assess potential patient and FC barriers to enrollment, we assessed their perceptions, knowledge, and information preferences about hospice. Methods: We conducted qualitative interviews with 16 adult patients with metastatic cancer and a prognosis ≤ 12 months and 8 of their FC. We used a semi-structured interview guide to elicit their perceptions (including perceived barriers to utilization), knowledge, and information preferences about hospice. Two raters coded interviews independently and reached acceptable inter-rater reliability (κ &gt; 0.85). We used content analysis to identify themes. Results: We found similar themes between patients and FC interviews. Participants had mixed views about which patients need hospice with some stating it is for patients only at the end-of-life and others perceiving it as important for patients who need care their family cannot provide. Notably, most patients perceived themselves as not needing hospice in the near future. While the majority perceived the role of hospice to enhance quality of life and provide comfort, some viewed it as providing practical support, including 24-hour care. 50% of participants had positive feelings about hospice, while others were more ambivalent. All participants felt they needed more information about hospice, yet they were mixed regarding the optimal timing of this information. Many thought it would be helpful to have information about hospice through pamphlets, websites, or videos, prior to a discussion with their oncologist. Most viewed denial and hope as the main barriers to early hospice enrollment. Conclusions: Study participants had misunderstandings about which patients were appropriate for hospice and regarding the services offered. Participants expressed strong desires for more information about hospice with educational tools, although were mixed about the optimal timing for reviewing these tools. These findings suggest that patients and FC would benefit from interventions to enhance their understanding of hospice and to facilitate a discussion with their oncologists.
The impact of surveillance imaging on overall survival in patients with recurrent Wilms tumor: A report from the Children’s Oncology Group.
Authors: E. A. Mullen, J. R. Anderson, K. J. Steacy, J. I. Geller, D. M. Green, P. Norkool, C. V. Fernandez, G. Khanna, M. H. Malogolowkin, J. Dome
Journal: Journal of Clinical Oncology (2011)

9536 Background: Surveillance imaging during and after therapy is employed to detect relapse in patients with Wilms tumor (WT). The use of more sensitive imaging modalities such as CT and MRI scans to supplement chest x-rays (CXR) and abdominal ultrasounds (US) may lead to early detection of relapse and improved survival. Concerns about the risk of cumulative exposure to radiation prompted us to assess whether the method of detection of relapse correlates with survival in patients with recurrent WT. Methods: Records were reviewed for 344 patients with recurrent unilateral WT who were enrolled on National Wilms Tumor Study-5 between 1995 and 2002. The reason for imaging (sign/symptoms versus routine surveillance), type of imaging, timing of relapse, site, maximum size and number of lesions, and interval from the last normal scan were recorded. These variables were analyzed with respect to 5-year overall survival (OS). Results: The estimated 5-yr OS from recurrence for all patients was 57%. 70% of relapses were detected on surveillance imaging, 25% with signs/symptoms, and 5% were not recorded. The estimated 5-yr OS was 62% when relapse was detected on surveillance imaging and 46% when relapse was detected symptomatically (p=0.024). For relapses detected by imaging, outcome differed depending on the number of tumor foci at relapse, with 5-yr OS estimates of 70%, 81%, 47%, and 29% for patients with 1, 2-3, 4-6, or > 6 foci (p<0.001). The interval from last normal imaging study was not greater in patients presenting with signs/symptoms or more disease foci (p=0.77), indicating that advanced disease state was not due to infrequent surveillance imaging. Among patients with recurrence detected by surveillance imaging, outcomes were slightly better when detection was by CXR/US (66% 5-yr OS) versus CT/MRI (56% 5-yr OS, p=0.06). Conclusions: The presence of signs/symptoms and multiple foci correlated with adverse outcome in patients with recurrent WT. Surveillance with CT/MRI scans was not associated with improved survival compared to surveillance with CXR/US. Tumor biology, rather than frequency or modality of surveillance imaging, appeared to be the primary determinant of outcome.