tbuckley/cabot-search huggingface dataset:
Transcriptomic profiles to differentiate colon and rectal adenocarcinomas.
Authors: John Hogan, Kathryn Dejulius, Xiaoxia Li, John Calvin Coffey, Matthew Kalady
Journal: Journal of Clinical Oncology (2014)

468 Background: Dissimilarity exists between colon and rectal cancer at a genetic, clinical, and molecular level. This is likely to reflect variation at a transcriptomic level. Transcriptional studies of colorectal cancer have previously combined colonic and rectal adenocarcinoma in a single group. Consequently few studies accurately describe the transcriptional profile of colon and/or rectal cancer. This study aims to develop classifiers based on transcriptomic differences between colon and rectal cancer and utilize these classifiers to predict tumor origin (colon vs. rectum). Methods: Comparisons were made between cDNA microarrays derived from colon (87) and rectal (125) adenocarcinomas. Gene expression data was filtered according to standard deviation to retain only highly dysregulated genes. Genes differentially expressed between colon and rectal adenocarcinoma were identified on two groups t test (p&lt;0.05, Bonferroni p value adjustment) and further analysed. Genes were rank ordered in terms of descending fold change. Comparisons included a) colon adenocarcinoma vs. rectal adenocarcinoma (stages I - III), b) stage II colon adenocarcinoma vs. stage II rectal adenocarcinoma and c) stage III colon adenocarcinoma vs. stage III rectal adenocarcinoma. For each comparison, those five genes with the greatest positive fold change were grouped in a classifier. Five separate tests were applied to evaluate the discriminatory capacity of each classifier and summary receiver operating characteristic curves generated for each classifier. Results: Genetic classifiers dervied from a comparison of stage II colon and stage II rectal adenocarcinoma were the most accurate in distinguishing tumor type (mean sensitivity 82.5%, mean specificity 81.7%). Classifiers derived from a pooled analysis comparing colon and rectal cancers (stages I - III) (mean sensitivity 79.8%, mean specificity 71.1%) and those derived from a comparison of stage III colon and stage III rectal cancers (mean sensitivity 57.1%, mean specificity 98.6%) were also accurate in determining tumor type (colon vs. rectum). Conclusions: Colon and rectal adenocarcinoma differs at a transcriptomic level. These findings provide insight into underlying biologic differences.
Hepatic imaging response to <sup>90</sup>y-microsphere therapy administered for tumor progression during systemic chemotherapy in patients with colorectal liver metastases.
Authors: Andrew S. Kennedy, David Ball, Steven J. Cohen, Michael Cohn, Douglas M. Coldwell, Alain Drooz, Edward Ehrenwald, Samir Kanani, Charles W. Nutting, Fred M Moeslein, Samuel G. Putnam, Steven C. Rose, Michael Savin, Sabine Schirm, Navesh K Sharma, Eric Wang
Journal: Journal of Clinical Oncology (2013)

270 Background: Hepatic tumor progression after one or more lines of 5FU-based systemic chemotherapy, with or without biologic agents, is an indication for radioembolization using 90 Y microspheres. Methods: An independent imaging review following resin-only 90 Y microsphere treated cases of mCRC from July 2002 to December 2011 at 9 US institutions was conducted. A board certified radiologist systematically reviewed hepatic Computed Tomography (CT) images (portal-venous phase) at baseline and 3 months after 90 Y treatment. Tumor response was assessed using RECIST 1.0 criteria, based on a maximum of 5 target lesions. Peri-tumoral edema and necrosis; known artifacts which can affect the interpretation of RECIST response, were documented for each lesion. Kaplan Meier analysis compared survival for responders [Partial Response (PR)] vs. non-responders [Stable Disease (SD) or Progressive Disease (PD)]. Results: A total of 184 patients were studied; male (61%) and Caucasians (61%) most common, mean age 62.5 years received a median of 2 (range 1–5) lines of chemotherapy prior to 90 Y therapy. Median tumor/liver ratio at 90 Y therapy was 15% (IQR 20%). Median 90 Y activity administered was 1.18 GBq (IQR 0.55). RECIST response at 3 months was 9.8% PR (n=18), 72.3% SD (133) and 17.9% PD (33); Disease Control Rate = 82.1%. Peri-tumoral edema was documented in 33% (n=60); necrosis in 42% (79); both in 22% (40) of cases, respectively. No significant differences in background characteristics between responders and non-responders were evident (p&gt;0.05). RECIST response at 3 months predicted survival: PR median 13.9 months (95% CI 9.2-30.3) vs. SD 11.0 (8.9-13.5) vs. PD 6.7 (5.5-8.1) [p=0.002]. Conclusions: Radiological lesion response to 90 Y therapy at 3 months must be interpreted with caution due to the significant proportions of peri-tumoral edema and necrosis encountered. Both of these artifacts may lead to either the under estimation of PR/SD or the overestimation of PD, respectively. Given these caveats, early (3 month) hepatic radiological response to 90 Y therapy appears to predict longer term prognosis.
Phase II study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III non-small cell lung cancer.
Authors: J. Y. Chang, R. Komaki, C. Lu, H. Y. When, P. Allen, A. S. Tsao, M. Gillin, R. Mohan, J. D. Cox
Journal: Journal of Clinical Oncology (2011)

7017 Background: Concurrent chemotherapy and radiotherapy to 60 to 66 Gy have been standard treatment for inoperable stage III non-small cell lung cancer (NSCLC) with median survival time of about 17 months and with more than 50% patients developing grade 3 toxicities. We sought here to improve the toxicity and survival in this group of patients by using proton-beam therapy to escalate the radiation dose to the tumor. We report early results of a phase II study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival. Methods: Forty-four patients with stage III NSCLC were enrolled our phase II clinical trial and treated with 74 Gy(RBE) proton therapy with weekly carboplatin (AUC 2) and paclitaxel (50 mg/m2). Disease was staged with positron emission tomography/computed tomography (PET/CT) and treatments were simulated with 4-dimensional CT to account for tumor motion. Protons were delivered as passively scattered beams and treatment simulation was repeated during the treatment process to determine the need for adaptive re-planning. Results: Median follow-up was 19.7 months (range, 6.1-44.4 months) and median overall survival was 29.4 months. No patient experienced grade 4 or 5 proton-related adverse events. The most common nonhematologic grade 3 toxicities were dermatitis (n=5), esophagitis (n=5), and pneumonitis (n=1). Nine patients (20.5%) experienced local disease recurrence but only 4 (9.1%) had isolated local failure. Four patients (9.1%) had regional lymph node recurrence but only one (2.3%) had isolated regional recurrence. Nineteen patients (43.2%) developed distant metastasis. The overall survival and progression-free survival rates were 86% and 63% at 1 year. Conclusions: High-dose proton therapy with concurrent chemotherapy is well tolerated and the 29.4-month median survival time and 20.5% total local failure rate are encouraging for inoperable stage III NSCLC. These findings lead to an ongoing prospective phase II randomized study comparing proton therapy vs. intensity-modulated (photon) radiation therapy to 74 Gy with concurrent chemotherapy for stage III NSCLC.
Hope, decision making, and use of the internet and other media among cancer clinical trials participants
Authors: F. J. Hlubocky, P. R. Helft, C. K. Daugherty
Journal: Journal of Clinical Oncology (2005)

6068 Background: While many cancer patients use the Internet to obtain information, little is known about the selected group of patients who enroll in clinical trials and if use of the Internet or other media is associated with decisions to enroll in a clinical trial. Methods: Advanced cancer patients (acp) enrolled in Phase I trials at the University of Chicago completed semi-structured interviews in order to describe their use of Internet and other media information (imi). We sought to describe: how often acp discuss imi with their doctors (mds), and associations between use of imi and validated measures of decision making preferences and level of hope. Results: 100 acp were interviewed; median age 62 (21–83); 56% male; 88% white; 43% high school education; 56% with colon cancer. 69% sought imi regarding treatment options. While 60% had internet access, only 30% reported actually using the internet for cancer-related information. 26% reported imi had an impact on their decision to enroll in a clinical trial. 42% stated that their hope was raised by imi. The more hopeful acp were, the less active they were in seeking imi (OR=0.439, p=0.026). 59% of those who sought imi discussed it with their mds. Acp provided imi by others were more likely to discuss this with their mds (OR=5.92, p=0.002). No association was found between acp’ preferences for decision making and whether they sought imi (OR=1.23, p=0.397). Education was associated with the likelihood of acp saying imi affected their decisions to seek experimental treatment (OR=1.18, p=0.045). Conclusions: The majority of acp participating in clinical trials use the internet and other media for information and discuss it with their mds. Less hopeful acp are more likely to use the internet and other media. Imi may play a role in sustaining acp hope about their disease. This information also plays a significant role in some acp’ decisions to enroll in a clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vitas Hospice
Neurocognitive function and psychological distress in young adults (YA) with cancer.
Authors: Kim Edelstein, Norma Mammone D'Agostino, Gregory Russell Pond, Sylvie Aubin, Andrew Matthew, Abha A. Gupta, Petr Kavan, Michael Crump, Philippe L. Bedard, Andre C. Schuh, David C. Hodgson, Kate Wahl, Rebecca Simpson, Te Vuong, Thierry Muanza, Gerald Batist, Lori J. Bernstein
Journal: Journal of Clinical Oncology (2016)

199 Background: Cancer treatment is associated with neurocognitive sequelae and changes in structural and functional brain imaging in older adults, even if they do not receive central nervous system directed therapy. Because the brain continues to develop into the 3rd decade of life, YA (age 18-39 yrs) may also be vulnerable to neurocognitive dysfunction. In YA, cancer disrupts acquisition of developmental milestones and is associated with psychological distress. This study aims to characterize neurocognitive functions and its relation to psychological distress in YA. Here we present baseline results of our longitudinal study. Methods: In this prospective, inception-cohort study, we recruited 3 groups of YA from ambulatory oncology clinics: YA with cancers (YAC; lymphoma, breast, gynecology, gastrointestinal, genitourinary, sarcoma) who required chemotherapy (YAC + , n = 55), YAC who do not require it (YAC - , n = 31), and healthy YA (HYA, n = 54). Participants completed a 2-hr battery of standardized neurocognitive tests and validated self-report questionnaires. YAC were assessed within 3 months of diagnosis, and YAC + prior to chemotherapy. Test scores were converted to age-corrected scaled scores and transformed to z-scores (mean 0, SD 1). A global neurocognitive function score and 6 domain scores were evaluated. Results: There were no group differences in neurocognitive domains (ANOVA, all p-values &gt; .1), or in the number of impaired test scores (defined as z &lt; -1). YAC + reported greater symptoms of somatic distress (p = .001) and anxiety (p = .004) than both HYA and YAC - . Symptoms were unrelated to neurocognitive performance (ρ &lt; .16 for all). However, each group had poorer memory compared to population norms (1-sample t-tests: YAC + p = .007; YAC - p = .047; HYA p = .023). Conclusions: Prior to treatment, neurocognitive functions of YAC were not different from HYA, suggesting that cancer itself is not a neurocognitive risk factor in YA. It is important to use appropriate control groups, rather than relying on normative data for comparison. We continue to follow this cohort to document neurocognitive function and distress over time, and to identify risk factors that contribute to outcomes in YA.
Expression of the epidermal growth factor receptor (EGFR or HER1) and human epidermal growth factor receptor 2 (HER2) in a large scale metastatic colorectal cancer (mCRC) trial
Authors: A. Adenis, E. Aranda Aguilar, Y. M. Robin, R. Miquel, F. Penault-Llorca, C. Castañón, B. Queralt, S. P. Eggleton, N. van den Berg, H. Wilke
Journal: Journal of Clinical Oncology (2005)

3630 Background: EGFR is commonly expressed in CRC (72–82%) and is therefore a target for anticancer therapies, such as the anti-EGFR monoclonal antibody cetuximab (Erbitux). There appears to be no correlation between tumor response to cetuximab and EGFR expression level. This may be due in part to co-expression of other ErbB receptors, such as HER2. The current results describe EGFR and/or HER2 expression in a population of CRC patients. Methods: In this large multi-center phase II study, patients with EGFR-expressing mCRC, who progressed on irinotecan-based treatment, receive cetuximab plus irinotecan. Immunohistochemistry on paraffin-embedded tumor material, obtained before recruitment into the trial, was used to assess EGFR and HER2 expression (defined as receptor membrane staining in > 0% of evaluated tumor cells). Results: Of 1206 tumor samples assessed for EGFR, 1034 (86%) were EGFR-expressing. Of a subgroup of 451 tumor samples tested for HER2, 292 (65%) were HER2-expressing: 253 (56%) expressed both EGFR and HER2, 120 (27%) expressed EGFR but not HER2, 39 (9%) expressed HER2 but EGFR was undetectable, and in 39 (9%) neither receptor was detectable. For all four subgroups, demographic and disease characteristics were similar, except that there were more rectal tumors in the EGFR-undetectable population (44% EGFR-undetectable vs. 30% EGFR-expressing). Conclusions: More than half of the CRC tumor samples assessed expressed both EGFR and HER2. HER2 expression was more common in the EGFR-expressing population compared with the EGFR-undetectable population. Evaluation of EGFR/HER2 co-expression as a potential predictor of the 12-week efficacy result will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA
Patterns of recurrence in 208 patients with Merkel cell carcinoma.
Authors: T. L. Bowles, M. I. Ross, M. S. Kies, V. Prieto, J. Myers, J. N. Cormier, P. F. Mansfield, J. E. Lee, J. E. Gershenwald
Journal: Journal of Clinical Oncology (2010)

8556 Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous tumor that has a propensity for locoregional and distant metastasis. Despite this overall aggressive biology, little is known regarding the patterns and extent of metastasis in these patients. Methods: The records of 208 patients (pts) with MCC who were treated between 1990 and 2006 at a single institution were reviewed. Tumor characteristics, treatment, and patterns of recurrence were documented. Median follow-up and time to recurrence were calculated. Results: Primary MCC tumors were most commonly located in the head and neck region (51%) followed by the extremities (40%). Primary tumor size was < 2.0 cm (ie, AJCC T1) in 74% of pts. In pts who underwent primary surgical resection with pathologic margin status known (n=151), 84% had a margin-negative resection. The majority of patients (77%) presented without clinical regional lymphadenopathy. At a median follow-up of 20 months, 87 (42%) of the 208 pts had thus far recurred. The median time to first recurrence was 8 months. Among these pts who recurred, sites of first recurrence were locoregional (local, intransit, and/or regional nodal), distant, or both in 70.1%, 25.3%, and 4.6% of pts, respectively. Regional nodes comprised the most common first site of recurrence (n = 36, 41.4%), the majority of whom had nodal disease only at first recurrence (n = 22). Among the 25 pts (28.7%) who developed distant metastasis as a first site of recurrence, 15 had visceral metastases. Liver and bone were the most common distant sites affected. While metastases to a spectra of visceral sites were observed, lung was an uncommon site (n = 4). Pts with distant disease at first recurrence were more likely to have primary tumors > 2.0 cm and clinically-positive regional nodes. Conclusions: Merkel cell carcinoma is characterized by frequent nodal and distant recurrences in the first year after treatment, emphasizing the importance of close surveillance after initial diagnosis and treatment. In contrast to melanoma, lung metastases are relatively uncommon, while liver and bone metastases are frequently observed. A better understanding of the patterns of treatment failure may help identify those patients most likely to benefit from adjuvant therapy. No significant financial relationships to disclose.
Immunologic response to xenogeneic gp100 DNA in melanoma patients: Comparison of particle-mediated epidermal delivery with intramuscular injection.
Authors: B. A. Ginsberg, J. D. Wolchok, R. Roman, H. F. Gallardo, P. B. Chapman, G. K. Schwartz, R. D. Carvajal, S. L. Terzulli, B. B. Bewkes, J. D. Yuan
Journal: Journal of Clinical Oncology (2010)

e13053 Background: Prior studies have shown intramuscular (IM) injection of xenogeneic orthologues of melanosomal antigens (tyrosinase, gp100) result in CD8+ T-cell responses to the syngeneic protein. To further define the optimal vaccination strategy, this clinical trial directly compared IM injection with particle-mediated epidermal delivery (PMED, also known as “gene gun” technology). Our hypothesis was that PMED would provide at least comparable immunogenicity using a substantially lower dose of DNA. Methods: Melanoma patients free of gross disease after surgery were randomized to either the PMED or IM arm and received 8 vaccinations over 4 months. Patients in the PMED and IM arms received 4 mg or 2000 mg per injection, respectively, of a mouse gp100 plasmid DNA vaccine. Blood samples were cultured with gp100 peptides and analyzed by tetramer and intracellular cytokine staining for responses to HLA-A*0201 restricted epitopes from the human gp100 gene. We defined a positive immune response as post-treatment T cell frequency 3 standard deviations above baseline. Results: Thirty-four HLA-A*0201+ patients with AJCC stage IIB-IV malignant melanoma were enrolled, with 27 completing all vaccinations and analyzable for immune response. The only common toxicity was grade 1 injection site reaction in 9 patients (26%), with no difference between arms, while a single dose-limiting toxicity of acute hypersensitivity occurred in the PMED arm in a patient with an undiagnosed gold allergy. Four of 27 patients (15%) had induction of gp100 tetramer+CD8+ T cells, all carrying the CCR7loCD45RAlo effector memory phenotype. Five of 27 patients (19%) had increased interferon-γ+ (IFN-γ) CD8+ T cells, one of which was also gp100 tetramer-positive. Overall, vaccination produced a measureable immune response in 8 of 27 patients (30%), which was not significantly associated with study arm or clinical outcome. However, there was a positive trend in the PMED group with increased generation of IFN-γ+ CD8+ T cells (p=0.07). Conclusions: A comparable efficacy and safety profile was demonstrated between the IM and PMED arms, despite a significantly decreased dose of DNA used for PMED injection. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PowderMed/Pfizer
Stimulation of B-CLL Cells with Interleukin 21 and Toll Like Receptor Agonists Induces a CTL-Like Transcriptional Profile.
Authors: Magdalena Hagn, Verena Ebel, Kai Sontheimer, Thamara Beyer, Sue E. Blackwell, Thomas Simmet, George J. Weiner, Bernd Jahrsdoerfer
Journal: Blood (2009)
Expression analysis of MET, EGFR, and HER2, and K-ras mutation status in patients with stage II/III gastric cancer enrolled in the ACTS-GC study.
Authors: Atsushi Ochiai, Koji Kitada, Wataru Ichikawa, Masanori Terashima, Issei Kurahashi, Hitoshi Katai, Ryoji Kushima, Mitsuru Sasako
Journal: Journal of Clinical Oncology (2013)

40 Background: Exploratory biomarker analysis was conducted to identify factors related to outcomes of patients enrolled in the ACTS-GC study, a randomized controlled trial comparing surgery followed by adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer. Methods: Formalin-fixed paraffin-embedded specimens obtained from 105 patients, an institutional subset of this biomarker study of 829 patients, were extensively examined for EGFR and HER2 by immunohistochemistry (IHC), MET amplification by FISH, and K-ras mutation status (codon 12, 13) by PNA-enriched direct sequencing. The expressions of 63 genes involved in pyrimidine metabolic pathway, growth factor signaling pathway, apoptosis, DNA repair, etc., were measured by quantitative real-time RT-PCR. The relations of the expressions of these genes to clinicopathological features such as histological type, T grade, N grade, tumor stage, gender, and age were also investigated. Results: The rates of K-ras mutation, EGFR overexpression, HER2 overexpression, and MET amplification were 6.7% (7/105), 14.3% (15/105), 11.4% (12/105), and 21.0% (22/105), respectively. These factors were almost mutually exclusive. Co-expressions were seen in 2 (EGFR &amp; HER2), 4 (HER2 &amp; MET), 5 (MET and EGFR) and 1 (EGFR &amp; HER2 &amp; MET) of the 105 patients. MET amplification and EGFR overexpression were associated with worse outcomes. In contrast, KRAS and HER2 status were not associated with overall survival or relapse-free survival. Expression levels of PCAM1, ESR1, MUC2, CAV1, ITGB3, and APC mRNA were significantly higher in diffuse-type cancer than in intestinal-type cancer, whereas expression levels of HER2, E2F1, LDHA and TOP2A mRNA were significantly higher in intestinal-type than in diffuse-type cancer (FDR P&lt;0.05). Associations of other clinically significant genes with clinicopathological features other than histologic type were not screened. Conclusions: Many clinical, pathological, molecular, and genetic factors have been investigated with a growing understanding of the molecular pathogenesis of gastric cancer. We review and discuss such prognostic markers in the ACTS-GC study.