tbuckley/cabot-search huggingface dataset:
Clinicopathological analysis of KRAS mutation in an Irish population.
Authors: M. Teo, S. O'Reilly, E. Moylan, D. G. Power
Journal: Journal of Clinical Oncology (2011)

467 Background: Clinical trials have shown that tumor KRAS status predicts response to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). We sought to compare distribution of wild-type and mutated KRAS in an Irish population and identify clinicopathologic correlates. Methods: From our prospectively maintained database we retrospectively identified patients with mCRC and documented KRAS status between Jan 2007 to June 2010. Medical notes were examined for patient demographics and disease characteristics. Variables were extracted and compared using unpaired t test and chi2 test. Results: 52 patients were identified, 29 (55.8%) with mutated (mt) and 23 (44.2%) with wild type (wt) KRAS from tumor tissue. Males accounted for 61.5% (n=31). Median age at diagnosis of metastatic disease for the KRASmt group was 66.4 years (range 56.7-82.1) and for the KRAS wt group was 64.2 years (40.1-76.8), p= 0.08. 21 (72.4%) of the KRASmt group and 16 (69.6%) of the KRASwt group had metastatic disease at presentation (p=0.81). For patients who presented initially with localised disease, time to development of metastases was 22.5mo (range 14-37.6) for the KRASmt group and 16.7mo (3.2-123.7) for the KRASwt (p=0.30). 21 (72.4%) of KRASmt and 17 (74.1%) of KRASwt tumors had left-sided primary (p = 0.84) with equal numbers of primary tumor resection in both groups. There was no statistical difference in TN-stage or the presence of liver metastases. Numbers of patients with KRASmt tumors with one, two and three or more different sites of metastases was 22 (75.9%), 5 (17.2%), and 2 (6.9%), and in KRASwt tumors there was no significant difference: 18 (78.3%), 4 (17.4%), and 1 (4.3%), respectively (p = 0.93). Median CEA at diagnosis for both groups were 19.7 μg/l (range 1.2-5958) and 6.1 (1.3-696.9; p = 0.11). Conclusions: We found that the ratio of KRASmt to KRASwt tumours in an Irish population is comparable to that in large international trials. Our analysis revealed no association between KRAS status and clinicopathologic variables. The inclusion of BRAF status, not readily available in our institution, may help define poor prognosis tumors. At present there is no validated molecular biomarker that is superior to standard clinicopathologic variables. No significant financial relationships to disclose.
Associations between symptom burdens (SB) and expectations of benefit (EB) for advanced cancer patients (ACP) and spousal caregivers (SC) participating in phase I trials.
Authors: F. J. Hlubocky, T. G. Sher, K. Wroblewski, M. J. Ratain, C. Daugherty
Journal: Journal of Clinical Oncology (2011)

e19595 Background: Terminally-ill ACP have been shown to have EB from experimental agents beyond what might be reasonably expected. The influence of disease severity and psychological factors, as measured by SB, on such EB is unknown. Methods: A convenience sample of ACP enrolling in phase I trials and SC were evaluated at baseline (T1) and one month later(T2) using a battery of standardized and/or validated assessments of SB including: cognition (MMSE); depression (CES-D); state-trait anxiety (STAI-S/T); posttraumatic growth (PTGI); quality of life/qol (FACIT-Pal); global health (SF-36); and martial adjustment (DAS). Data re participant EB were obtained utilizing Likert scores (1-10) measuring the likelihood of chemotherapy in: “stabilizing” (ST), “halting/shrinking” (HL), producing “remission”(PR), and “curing” (C) ACP’s cancer. Results: 104 participants (52 Phase I ACPs and 52 SC) were separately interviewed at T1 and T2. For the population as a whole, median age was 61y (28-78y); 50% male; 100% married; 87% Ca; 67% >HS educ; 51% GI dx. No associations were found between ACP SB (MMSE, CES-D, STAI-T, PTGI, FACIT-Pal, SF-36, DAS) and EB reported by ACPs. Regression analyses at T2 revealed negative associations between ACP SB state anxiety scores and the following ACP EB: ST, F (1, 51) = 6.52, p=.01; HL, F (1, 51) = 8.44, p< .01; and to PR of disease, F (1, 51) = 4.30, p=.04. At T2, for SC, negative associations were found between SC state anxiety and SC EB for: ST cancer, F (1, 51) = 6.52, p=.01, and HL, F (1, 51) = 3.02, p<.01. SC trait anxiety was also negatively associated with SC EB for ST the ACP’s cancer, F (1, 51) = 5.46, p=.02. Regression analyses revealed positive associations between SC martial satisfaction scores and the following SC EB: ST, F (1, 51) = 4.14, p=.04; HL, F (1, 51) = 4.46 p=.04; PR, F (1, 51) = 4.39, p=.04; C, F(1, 51) = 4.22, p=.03. Further positive associations were found between SC EB HL cancer and SC SF36 scores, F(1, 51) = 3.97, p=.03. No additional associations were found between SC SB (MMSE, CES-D) and SC EB. Conclusions: Our data indicate that several significant associations exist between ACP and SC SB and EB from Phase I trial participation.
Optimal timing for curative surgery after preoperative chemoradiotherapy in locally advanced rectal cancer.
Authors: Yoo-Kang Kwak
Journal: Journal of Clinical Oncology (2016)

677 Background: This study is a multicenter retrospective analysis conducted by the Korean Radiation Oncology Group (KROG) to identify the optimal operation timing after preoperative chemoradiotherapy (CRT) in rectal cancer. Methods: The study included data of 1786 patients who were diagnosed with locally advanced rectal cancer (cT3-4N0-2M0) and received preoperative CRT followed by curative surgery from 2003 to 2014, at 8 institutions in Korea. Total radiation dose was 50.4 Gy in 28 fractions, delivered in 1.8 Gy per fraction. All patients received total mesorectal resection. Interval time between preoperative CRT and surgery ranged from 1 week to 136 weeks, and median interval time was 7 weeks. Downstaging rate was assessed by comparing clinical pre-CRT and pathological post-CRT stages and downstaging was defined as ypStage 0-I (ypT0-2N0M0). Pathologically complete response (ypCR) was defined as the complete absence of viable tumor (ypT0N0M0). Primary end point of this study was to evaluate the period of highest downstaging and ypCR rates to determine the optimal timing for surgery after CRT. Results: Analyses on downstaging and ypCR rates were done with all patients. Downstaging rates peaked between 6 and 7 weeks and declined afterwards. ypCR rates increased from 5 to 6 weeks and decreased after 9 to 10 weeks. The patients were divided into two arms according to the median interval time between preoperative CRT and surgery. Downstaging rates were similar between the two arms showing 36.9% in the early arm (≤ 7 weeks) and 37.0% in the delayed arm ( &gt; 7 weeks). However, ypCR rates were significantly higher in the delayed arm, compared to the early arm (12.3% vs. 8.6%, p = 0.011). Complete tumor regression was superior in the delayed arm, as compared to the early arm (13.2% vs. 9.1%, p = 0.004). The delayed arm had higher sphincter preservation rates than the early arm with a marginal significance (92.4% vs. 89.9%, p = 0.078). There was no statistically significant difference regarding overall survival and disease-free survival. Conclusions: The optimal timing for surgery for advanced rectal cancer is after 7 weeks and before 10 weeks following preoperative CRT.
Use of tumor-mediated TRAIL-receptor expression to evaluate apoptotic depletion of infiltrating CD8+ immune cells in clinical colorectal cancer.
Authors: A. Waaga-Gasser, M. Grimm, M. Kim, A. Rosenwald, C. T. Germer, M. Gasser
Journal: Journal of Clinical Oncology (2010)

e21038 Background: Expression of apoptosis-related proteins on tumour cells has been shown in several experimental models to be an efficient mechanism for a counterattack against host antitumour immune responses in solid tumours. Here we provide clinical evidence for such a tumour immune escape mechanism by demonstrating tumour to T cell directed death receptor signalling (TRAIL/TRAIL-R) in colorectal cancer (CRC). Methods: In a series of patients with CRC and completed 5-year follow up we investigated apoptosis and expression levels of apoptosis-related proteins. Results: Elevated soluble TNF-receptor 1 and 2 levels were found in sera during tumour progression as one of the tumour immune escape mechanisms in the patients. Gene and protein profiles in the tumours demonstrated intratumoral upregulated gene expression for Fas, FasL, TRAIL, TRAIL-R, and TNF-a (RT-qPCR). Levels of TUNEL-positive events were positively correlated with TRAIL-R1-expression on tumour infiltrating immune cells. Among the immune cells, preferentially CD8+ T cells were found to express TRAIL-R1 while serial immunostaining in the same patient tumours showed abundant apoptotic (TUNEL-positive) immune cells. Conclusions: Our results in tumour samples from CRC patients suggest TRAIL-R1-mediated apoptotic depletion of infiltrating immune cells (CD8+) in response to TRAIL expression by the tumour itself. This supports the notion of an efficient escape from tumour immune response and thus evasion from the attack of activated CD8+ T cells. These findings may enhance our understanding of tumour progression in CRC and might be helpful for the development of TRAIL and its death receptor-based therapy. No significant financial relationships to disclose.
Racial differences in patients with hepatocellular carcinoma: A large single-institution experience.
Authors: Neeta K. Venepalli, Tad D. Nair, Stephanie A. Berg, Mary Modayil, Ron C. Gaba, James T. Bui, Yue Huang, Scott Cotler
Journal: Journal of Clinical Oncology (2013)

318 Background: Hepatocellular carcinoma (HCC) disproportionately affects minorities with higher age-adjusted incidence and mortality rates in Hispanics (H) and blacks (B) versus non-Hispanic whites (C). While H have the fastest rising rates of HCC of all ethnic groups per SEER analysis, little is known about race specific risk factors and disease characteristics. Methods: We retrospectively reviewed HCC patients (pts) treated at University of Illinois-Chicago between 1998 and 2005. Demographics, disease characteristics, treatment patterns, and survival were analyzed with descriptive statistics and chi-square p values. Results: Mean age of HCC pts (N=195) at diagnosis was 59.7 years + 9.8 (19.5% female; 22% aged 65 or older; 61.5% Medicare or Medicaid; 4.1% without insurance; 22.6% H; 31.2% B). Compared to C and B, H pts were more likely to have ascites and NASH and less likely to have ever smoked or have hepatitis C. Compared to B, H pts were more likely to have metabolic syndrome, diabetes, and encephalopathy (HE). Compared to C, B pts had lower MELD scores. Conclusions: In our patient population, Hispanic patients were significantly more likely to have diabetes and NASH, and lower frequency of tobacco use, HCV, and elevated AFP levels at diagnosis. [Table: see text]
Bortezomib Induced Thrombocytopenia Might Be Due to the Inhibition of Proplatelet Formation of Megakaryocyte.
Authors: Kazunori Murai, Shugo Kowata, Akiko Abo, Tatsuo Oyake, Kenichi Nomura, Shigeki Ito, Yoji Ishida
Journal: Blood (2010)
Phosphatase PRL2 promotes AML1-ETO-induced acute myeloid leukemia
Authors: M Kobayashi, S Chen, Y Bai, C Yao, R Gao, X-J Sun, C Mu, T A Twiggs, Z-H Yu, H S Boswell, M C Yoder, R Kapur, J C Mulloy, Z-Y Zhang, Y Liu
Journal: Leukemia (2017)
Urinary obstruction following stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer.
Authors: W. Tristram Arscott, Leonard Chen, Nathan Wilson, Aditi Bhagat, Joy S. Kim, Thomas M. Yung, Siyuan Lei, Brian Timothy Collins, Simeng Suy, Anatoly Dritschilo, John H. Lynch, Sean P. Collins
Journal: Journal of Clinical Oncology (2014)

196 Background: Obstructive urinary symptoms are common following prostate cancer treatment with radiation therapy. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT obstructive urinary symptoms would be more severe. This study sought to evaluate obstructive urinary symptoms and urinary retention requiring catheterization following SBRT for prostate cancer. Methods: Patients treated with SBRT monotherapy for localized prostate cancer from August 2007 to July 2011 at Georgetown University Hospital with a minimum of two years of follow-up were included in this study. Treatment was delivered using the CyberKnife with doses of 35 Gy to 36.25 Gy in five fractions. Urinary retention was recorded and scored using the CTCAE v.4. Patient-reported urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) before treatment and at months 1, 3, 6, 9, and 12 and every six months thereafter. Results: Two hundred sixty nine patients at a median age of 69 received SBRT with a median follow-up of three years. Prior to treatment, 32.1% of patients utilized alpha-antagonists and 17.8% were dissatisfied with their urinary function. The two-year actuarial incidence rates of acute and late urinary retention greater than or equal to grade 2 were 39.5% and 41.4%. Alpha-antagonist utilization rose at one month (57.9%) and 18 months (48.0%) post-treatment. However, grade 3 urinary retention was low with four men (1.5%) requiring catheterization and/or transurethral resection of the prostate. A mean baseline IPSS obstructive symptom score of 3.6 significantly increased to 5.0 at one month (p &lt; 0.0001), however returned to baseline at three months (p = 0.74). Late IPSS increases were common, but transient. The IPSS obstructive symptom score returned to baseline in 79.6% of patients by six months and 92.6% by two years. Dissatisfaction with urinary function declined to 14% by two years post treatment (p &lt; 0.05). Conclusions: Treatment of prostate cancer with SBRT resulted in an acute increase in obstructive urinary symptoms, which peaked at one month post-treatment. However, the risk of acute urinary retention requiring catheterization was low. Obstructive urinary symptoms returned to baseline in the majority of patients by six months and in more than 90% by two years.
The relationship of magnetic resonance (MR) imaging characteristics with race.
Authors: Jennifer Chun, Freya Ruth Schnabel, Shira Schwartz, Chelsea Marin, Amber Azniv Guth, Deborah M. Axelrod, Richard L. Shapiro, Daniel F. Roses, Linda Moy
Journal: Journal of Clinical Oncology (2015)

10 Background: Research has shown that women of different race have differences in tumor biology. Previous studies have shown that mammographic breast density (BD) and background parenchymal enhancement (BPE) are associated with breast cancer risk. There is data on the relationship of race and BD, but a dearth of information on the relationship of race and MR imaging characteristics such as fibroglandular tissue (FGT) and BPE. The purpose of this study was to evaluate the relationship of race with BD, BPE, and FGT in women with breast cancer. Methods: The institutional Breast Cancer Database was queried for all women with newly diagnosed breast cancer from 2010-2015. Variables included age, race, body mass index (BMI), imaging and tumor characteristics. Statistical analyses included Pearson’s Chi Square Tests. Results: A total of 2,092 women were included in this analysis. The median age was 59 years (range 22-95). Majority of patients had invasive ductal carcinoma (62%), early stage (0, I) tumors (71%), ER-positive (84%), PR-positive (71%), and HER2-negative (86%). However, there was a higher proportion of later stage (p &lt; 0.0001) and triple negative (p = 0.002) disease among blacks. Compared to whites, blacks had higher BMI, lower BD and lower BPE, while Asians had lower BMI &lt;, higher BD, higher FGT and higher BPE (see table). Conclusions: As previously described, we found differences among races with respect to tumor histology. However, the differences in imaging characteristics between races are likely accounted for by differences in BMI and may not be directly related to breast carcinogenesis. [Table: see text]
Differences between colon cancer primaries and metastases utilizing a molecular assay for tumor radiosensitivity and implications for potential oligometastatic SBRT patient selection.
Authors: Kamran A. Ahmed, William J. Fulp, Anders E. Berglund, Sarah E. Hoffe, Thomas J. Dilling, Steven A. Eschrich, Ravi Shridhar, Javier Torres-Roca
Journal: Journal of Clinical Oncology (2015)

569 Background: We have previously identified a multigene expression model of tumor radiosensitivity with validation in four independent cohorts (breast, rectal, esophageal, and head and neck). This model predicts a radiosensitivity index (RSI) that is directly proportional to tumor radioresistance, (RSI, high index = radioresistance). The purpose of this study was to assess differences in RSI between primary colon cancer and metastases. Methods: Patients were identified from our institutional IRB-approved prospective observational protocol. A total of 704 metastatic and 1,362 primary lesions were obtained from a de-identified meta-data pool. Gene expression was obtained from Affymetrix Hu-RSTA-2a520709 microarrays. RSI was calculated using the previously published ranked based algorithm. An independent cohort of 38 lung and liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiotherapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors compared with 54% of primaries were in the RSI-radioresistant (RSI-RR) peak, suggesting that metastatic tumors may be slightly more radioresistant than primaries (p=0.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radioresistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31), p&lt;0.0001. These findings were confirmed when the analysis was restricted to lesions from the same patient (n=69). In our independent cohort of lung and liver metastases, lung metastases had an improved outcome over patients with liver metastases (2 yr local control, lung vs. liver metastases; 100% vs. 74.0%, p=0.027). Conclusions: Assessment of radiosensitivity between primary and metastatic tissues of colon cancer histology, reveals significant differences based on anatomical location of metastases. These initial results warrant validation in a larger clinical cohort.
Developing a virtual collaborative to facilitate palliative care and quality improvement learning in oncology.
Authors: Arif Kamal, Kristen McNiff, Ann A. Prestrud, Dale Lupu, Molly Gavigan, Yousuf Zafar, Richard L. Schilsky, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2013)

252 Background: Despite a strong evidence base and increasing calls for integration, oncologists find it difficult to deliver primary palliative care concurrent with standard oncology care. Solutions that promote practical integration of palliative care in oncology are needed. In an AHRQ-funded pilot, ASCO and the American Academy of Hospice and Palliative Medicine are developing the Virtual Learning Collaborative (VLC) to develop and test a scalable model for quality improvement and dissemination of best practices in palliative care within the oncology setting. Methods: The VLC will be a web-based learning and collaboration system built upon existing ASCO technology resources. We will select at least 25 oncology practices to participate in regular, facilitated learning sessions, collaborative discussions, and sharing of best practices. The VLC will equip each practice with the knowledge, tools, and coaching to select, test, and adopt a quality improvement intervention relevant to their own palliative care needs. Development of the VLC is ongoing; oncology practices begin participation in Spring 2014. Results: We will assess the VLC using protocol-driven evaluation methods common to technology development, quality improvement, implementation science, and educational initiatives. VLC usability, feasibility, and acceptability will be assessed through surveys of participating practices and focus groups. Longitudinal changes in conformance to palliative care metrics will be assessed using ASCO’s Quality Oncology Practice Initiative (QOPI) system. We will use mixed qualitative and quantitative evaluation methods to assess ongoing changes in clinician knowledge and self-efficacy in applying palliative care principles. Conclusions: We aim to develop and test a novel method for facilitating quality improvement and palliative care learning in oncology. Through this pilot, we will refine the VLC for implementation in the greater oncology community. Ultimately, this effort supports other ASCO and AAHPM quality improvement initiatives focused on clinician education and dissemination of best practices.
Effect of prior abiraterone (ABI) or enzalutamide (ENZ) on sipuleucel-T (sip-T) manufacture in PROCEED patients (pts).
Authors: Nicholas J. Vogelzang, Jeffrey L. Vacirca, Philip W. Kantoff, Mark C. Scholz, Shaker R. Dakhil, Luke T. Nordquist, Celestia S. Higano, A. Oliver Sartor, Matthew R. Cooperberg, Andrew Sandler, Candice McCoy, James Boyd Whitmore, Robert Claude Tyler, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2014)

185 Background: Sip-T is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). PROCEED is an ongoing phase 4 registry, enrolling pts receiving commercial sip-T. There are no exclusions based on prior prostate cancer treatments, so sip-T product parameters can be evaluated in pts receiving prior hormonal agents such as ABI or ENZ. Methods: Pts treated with sip-T within ≤6 mo were eligible to provide informed consent. Prior anticancer interventions were recorded at baseline. Sip-T product parameters were assessed. Results: Of 1,376 pts (as of May 2013), 108 (7.8%) received prior ABI and 58 (4.2%) received ENZ. Patients with ABI or ENZ generally had more advanced disease vs. pts without prior ABI or ENZ (WPT) and a greater proportion of the ABI and ENZ pts received prior docetaxel. There were slight differences in some sip-T product parameters in the ABI and ENZ groups, but neither manufacture nor receipt of sip-T were inhibited, as indicated by the percentage of pts with 3 successful infusions. All groups showed evidence of immune prime boost (Table). Conclusions: A subset of patients in PROCEED have received ABI or ENZ prior to sip-T. We observed no impact of prior ABI/ENZ on sip-t manufacturing or delivery, despite these men having more advanced disease. These results are consistent with prior analyses demonstrating a positive sip-T treatment immune effect in patients who have received prior therapies, including chemotherapy. Further immune monitoring and outcome studies are currently ongoing in the pre-docetaxel mCRPC setting where these agents will likely be used clinically. Clinical trial information: NCT01306890. [Table: see text]