tbuckley/cabot-search huggingface dataset:
Evaluation of the frequency of c-Met and HER2 expressions in gastric carcinoma and their association with clinicopathologic factors.
Authors: Suayib Yalcin, Yetkin Yildiz, Cenk Sokmensuer
Journal: Journal of Clinical Oncology (2014)

72 Background: Met and HER-2 protoonkogenes encode a receptor tyrosin kinase c-Met and HER-2. We aimed to determine the frequency of c-Met and HER-2 overexpression in gastric cancer and investigated their association with clinicopathological factors. Methods: Patients withstage I-IV disease were analyzed. Overexpressions of c-Met and HER-2 were determined with immunohistochemistry. Results: A total of 143 patients, 97 male 46 female were enrolled. C-Met score was 3 (+) in 31.5 %, 2 (+) in 27.3% and 1 (+) in 10.5% of the patients. There was no statistically significant differences in age, sex, tumor location, differentiation, Lauren classification, TNM staging, presence of distant metastasis, depth of tumor invasion (T), lymphovascular invasion, and survival between c-Met subgroups. HER-2 was 3(+) in 9.1%, 2(+) in 9.8%, and 1(+) in 16.1% of the patients. HER-2 overexpression was associated with better differentiation, intestinal subtype and advanced stage. C-Met overexpression was 84.6% in HER-2 3(+), 64.3% in HER-2 2(+), 69.6%, HER-2 1 (+) and 51.6% in HER-2 (-) patients. There was no statistically significant difference in survival between the c-Met overexpression positive and negative Stage III and IV patients. The median survival was 11.6 ± 6.3 months in HER-2 overexpression positive Stage IV patients and 11.9±6.8 months in HER-2 overexpression negative stage IV patients. There were no statistically significant differences in survival between the two groups. Conclusions: There is an association between c-Met positivity and HER-2 overexpression. C-Met was not associated with any negative prognostic factors in gastric cancer.
Factors associated with delayed time to adjuvant chemotherapy (AC) in stage III colon cancer: British Columbia Cancer Agency (BCCA) cohort experience.
Authors: A. Chan, R. Woods, S. Gill
Journal: Journal of Clinical Oncology (2011)

e16603 Background: The current standard for stage III colon cancer after resection is adjuvant 5FU-based chemotherapy. In trials, AC is mandated within 8 weeks after surgery, but this is not always the case outside the clinical trial setting. A recent meta-analysis confirms that AC started more than 8 weeks after curative surgery results in significantly decreased overall survival. Our objective was to ascertain logistical and patient factors associated with delayed delivery of AC (defined as >56 days from date of surgery) in referred patients with resected stage III colon cancer. Methods: A population-based cohort of patients diagnosed with stage 3 colon cancer between January 2008 to December 2009 referred to the BCCA and treated with at least one cycle of AC were identified. Patient characteristics, and event-specific time intervals between surgery, referral, medical oncology consultation (MOC) and AC were assessed. Differences in patient characteristics and event intervals between patients who received delayed and timely chemotherapy were assessed using the Chi-square and Wilcoxon Rank-sum tests. Results: Median time from surgery to AC was 58 days with 54% of patients receiving AC beyond 56 days. Temporal differences were identified in all event intervals between the between the timely and delayed groups (see table). Referral was most commonly initiated after hospital discharge The only patient factors associated with delayed initiation included poorer ECOG status and being treated at the most urban centre within BCCA. Age, gender, comorbidity index, T stage and tumour location were not different between the groups. Conclusions: 54% of patients with stage III colon cancer had delayed AC initiation. Process related delays at each step of the referral process need to be addressed including timely referral, MOC triage and addressing chemotherapy waitlists. Time to chemotherapy Event interval Statistic All cases ≤56 days >56 days P value Surgery to referral (days) N 370 164 206 Median 15 12 18 p<0.0001 Referral to med onc N 349 156 193 consult (days) Median 21 17 23 p<0.0001 Med onc consult to N 395 182 213 chemotherapy (days) Median 20 14 26 p<0.0001
First human dose (FHD) study of the oral transforming growth factor-beta receptor I kinase inhibitor LY2157299 in patients with treatment-refractory malignant glioma.
Authors: J. Rodon Ahnert, J. Baselga, E. Calvo, J. Seoane, I. Brana, E. Sicart, I. Gueorguieva, A. Cleverly, M. M. F. Lahn, S. Pillay, M. Holdhoff, J. O. Blakeley, M. A. Carducci
Journal: Journal of Clinical Oncology (2011)

3011 Background: Activated TGF-b signaling has been associated with poor survival in several tumors, including glioma, hepatocellular and pancreatic cancer. TGF-b inhibitors are expected to improve outcome in such cancer patients. We report on safety, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of intermittent treatment with the TGF-b inhibitor LY2157299. Methods: Using a predictive pre-clinical PK/PD model and after evaluating safety of continuous dosing at 40 and 80mg/day (Calvo-Aller et al. 2008 ASCO 14554), patients were treated at 160, 240 and 300mg/day with intermittent dosing (14 days on followed by 14 days off) to determine the biologically effective dose (BED) for Phase 2. Together with standard evaluation, cardiac safety was assessed. PK, PD and tumor response evaluation were documented. Each cohort enrolled at least 6 with expansion to 12 evaluable patients if PK profile was inconclusive. Results: 28 patients with Grade IV glioma were treated and LY2157299 was well tolerated at all doses. There were two drug-related dose limiting toxicities, a pulmonary embolism and thrombocytopenia in cycle 2. No medically significant cardiotoxicities were observed. Three patients taking 160 mg/day were treated for >20 cycles. There were 3 confirmed, 1 unconfirmed PR at 160 mg/day and 1 unconfirmed PR at 300 mg/day. LY2157299 was rapidly absorbed with elimination half-life of approximately 6.5 hours. AUC(0-∞) at steady state was dose proportional for any two-fold increase in dose between 40 to 300mg. Within and between patient coefficients of variation were 26% and 40%, respectively. In some patients PD effects (e.g., pSMAD in PBMC) indicated target inhibition starting at the 160mg/day dose level. Conclusions: The 14 days on/ 14 days off treatment is safe at all dose levels and MTD was not observed at the anticipated maximum BED of 300mg/day. Notably, the BED range is above 160 mg/day showing anti-tumor response in at least 3 patients with durable responses beyond 1 year. Given the overall safety profile and interesting anti-tumor effect, LY2157299 is being investigated in phase II studies.
A clinical care pathway to improve the acute care of patients with glioma.
Authors: Natalie Riblet, Jennifer Snide, Evelyn Schlosser, David Nalepinski, Lanelle Jalowiec, Lara Kunschner Ronan, Linda Mason, Nancy Kennedy, Sabrina Powers, Tobi Cooney, Katherine Thorley, Camilo E. Fadul
Journal: Journal of Clinical Oncology (2014)

217 Background: Gliomas account for nearly 80% of primary malignant brain tumors and are associated with poor survival. Developing clinical care pathways to ensure that patients receive coordinated, comprehensive and timely care may result in improved outcomes and patient satisfaction. Methods: A quality improvement (QI) project was chartered to improve the care provided to patients with glioma. A multidisciplinary team was convened and met weekly and then monthly from Feb 2013 – April 2014. Twenty best practice measures were identified from the literature. Using a Plan-Do-Study-Act framework, the team brainstormed and implemented various improvement interventions between Oct 2013 and Feb 2014. Statistical process control charts were used to evaluate progress. A dashboard of quality measures was generated to allow for ongoing reporting. Results: Retrospective data was available for 12 best practice measures; 6 of which could be abstracted from electronic medical records. Eight measures were not part of the current system of care. The baseline population consisted of 98 patients with gliomas. Review of their records suggested wide variation in performance, with compliance ranging from 30% to 100%. Unanticipated opportunities for improvement included a high proportion of outpatient falls (7%) and urinary tract infections (10%). The team hypothesized that lack of standardization in the current process may contribute to less-than-ideal performance. After implementing improvement interventions, the records of 19 consecutive patients with glioma were reviewed. The proportion of patients meeting criteria for 12 practice measures modestly improved (65% pre QI-work; 78% post-QI work). There were no additional cases of urinary tract infections. Barriers to pathway development included difficulties with transforming manual measures into electronic data sets and accounting for portions of care that occurred at outside facilities. Updated outcomes will be presented. Conclusions: Creating evidence based clinical care pathways for addressing the acute care needs of patients with glioma is important. There are many challenges, however, to developing sustainable systems for measuring and reporting performance outcomes overtime.
Somatic Mutations and Inborn Variants in Exon 12 of ASXL1 in Different Myeloid Neoplasms
Authors: Susanne Schnittger, Christiane Eder, Annette Fasan, Thomas Illig, Norman Klopp, H.-Erich Wichmann, Wolfgang Kern, Claudia Haferlach, Torsten Haferlach
Journal: Blood (2011)
Risk factors associated with overall survival (OS) in recurrent pancreatic adenocarcinoma (PAC) following curative resection (CR).
Authors: Daniel H. Ahn, Chul Ahn, Kavya Krishna, Somashekar Krishna, Peter Muscarella, Mark Bloomston, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2015)

437 Background: Patients (pts) with localized pancreas cancer (LPAC) undergo CR with curative intent. Despite improvements in adjuvant treatment (trmt) and surgical techniques, the majority of pts succumb to recurrent disease (dx). The purpose of this study is to identify risk factors associated with OS in pts with recurrent PAC. Methods: Pt clinical and dx data was obtained by a retrospective review of patients with LPAC who underwent CR from 2004-2012 and had recurrent dx. Pts were subdivided into two groups, time to recurrence less/equal or greater than 6 months. Univariate and multivariate Cox regression models were used to determine the association between pt characteristics and OS. Results: 93 pts were identified with recurrent PAC. Select pt characteristics are listed in the Table. In univariate Cox models, only lymph node (LN) status is significantly associated with OS (HR 01.67; p=0.043). OS was 25.6 months (95% CI, 19.4-25.6) for LN positive tumors and 10.6 months (95% CI, 10.6-20.1) for LN negative tumors. In a multivariate Cox model adjusted for pt characteristics, LN status remained significant for OS (HR=1.67; p=0.043). Pts with early recurrent PAC (≤6 month) seem to follow patterns of distant metastatic dx while pts with later recurrence that of locoregional dx. Conclusions: LN involvement is associated with patterns of early recurrence with predominantly metastatic disease and decreased OS in pts with recurrent PAC. LN status may act as a surrogate marker for pattern of recurrence and merit consideration in the selection, stratification and trmt of patients in clinical trials. After CR, LN involvement may influence choice trmt and warrant more aggressive therapy. [Table: see text]
Comparison of the quality of life of early and advanced stage ovarian cancer survivors
Authors: K. Mirabeau-Beale, A. B. Kornblith, R. T. Penson, H. Lee, A. Goodman, S. M. Campos, L. R. Duska, L. Pereira, C. D. Gibson, U. A. Matulonis
Journal: Journal of Clinical Oncology (2008)

5528 Background: No direct quality of life (QOL) comparisons have been performed based on ovarian cancer staging. The objective of this study was to compare the long-term adjustment and QOL of both early and advanced stage ovarian cancer survivors (OCS). Methods: Early and advanced OCS were identified from patient logs. All patients were >3 years from diagnosis and had no evidence of recurrent cancer. Patients were interviewed by phone or in clinic, and the following surveys were administered: EORTC QLQ-C30 (EORTC) and QLQ-OV28 (OV-28), MHI-17, CALGB sexual functioning, FACT Fatigue, Beck’s Hopelessness, Fear of Recurrence (FOR), PCL-C post-traumatic stress disorder (PTSD), Unmet Needs, FACT-Spirituality (FACT-Sp), complementary therapy use, and MOS Social Support (MOS). Overall QOL and long-term physical, mental, and sexual effects were compared between the early and advanced stage groups. Results: 58 early stage and 42 advanced pts were interviewed. Except for social functioning (EORTC-social functioning, p< .05;), there were no differences in physical symptoms, functioning and psychological state between the two groups. Anxiety when getting CA125 tested was reported by 59% of early stage and 64% of advanced stage survivors. The percent of survivors scoring at the norm or greater on the MHI Index was 71% for early stage survivors and 64% for advanced stage survivors. The following variables did not differ significantly between the two groups: overall quality of life (EORTC), fatigue (FACT), hopelessness (BECK), spirituality (FACT-Sp), social support (MOS), unmet needs and use of complementary therapy. Psychological assessment revealed that 26% of both the early and advanced OCS had scores indicative of PTSD (PCL-C). Decreased sexual interest attributed to cancer was reported by 54% of early stage and 31% of advanced stage survivors, while 40.5% early stage and 46% advanced stage survivors reported decreased sexual activity attributed to cancer. Conclusions: Long-term QOL and adjustment appear to be independent of initial stage. PTSD and sexual disinterest are important issues for OCS of both early and advanced stage patients in remission. No significant financial relationships to disclose.
Perspectives on electronic health information exchange among people affected by cancer.
Authors: E. B. Beckjord, R. Rechis, L. N. Shulman, B. Hesse
Journal: Journal of Clinical Oncology (2011)

6123 Background: We know little about the people’s attitudes towards electronic health information exchange (EHIE) and less about whether these attitudes differ between healthy individuals and those affected by cancer. A better understanding of these attitudes will help to keep EHIE policy and practice patient-centered. Methods: We used two data sources to investigate perspectives on EHIE; a 2010 survey fielded by LIVESTRONG (the Lance Armstrong Foundation) on EHIE from individuals across the cancer care trajectory (n=7,417) and results from the National Cancer Institute’s 2007 Health Information National Trends Survey (HINTS) providing the same perspectives from the American public. Results: See table. Regarding capabilities of electronic health records (EHR), nearly all respondents to the LIVESTRONG survey “strongly agreed” that privacy is important; more than 70% want EHRs to make information sharing with providers more convenient. Many want to enter their own physical and emotional symptoms into the EHR. Finally, respondents have high confidence that EHIE will improve the quality of their health care. Conclusions: People affected by cancer appear to be eager to leverage EHIE to improve quality of care, facilitate information exchange between their providers, actively self-enter personal data, and have their de-identified data contribute support research. Cancer pts on Rx (n=433) Pts living with active cancer (n=298) Post-treatment survivors (n=2343) No personal hx of cancer (n=4343) American public (HINTS 2007) “Very important” that my health care providers are able to share my medical information with each other electronically 79.8% 82.1% 75.4% 68.7% 47.9% “Very important” that I can get my own medical information electronically 75.1% 81.1% 70.8% 69.8% 51.7% “Strongly agree” that researchers should be able to use my medical information if de-identified 59.4% 70.4% 60.0% 55.6% 32.4%
Evaluation of the neutrophil-lymphocyte ratio (NLR) during neoadjuvant chemotherapy (NC) for muscle-invasive bladder cancer (MIBC) and correlation with pathologic response to treatment.
Authors: Jo-An Seah, Raya Leibowitz-Amit, Eshetu G. Atenafu, Nimira Alimohamed, Anthony Michael Joshua, Jennifer J. Knox, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2014)

351 Background: Cancer associated inflammation, as measured by markers such as NLR, appears to impact on outcome. In MIBC, an elevated NLR&gt; 2.5 prior to radical cystectomy (RC) is associated with a poorer prognosis (Gondo, 2011). We evaluated the pattern of change in NLR before (pre-NC), during (mid-NC) and after NC (pre-RC) and correlated this with pathological outcomes, to determine if NLR is of predictive value in this setting. Methods: AllMIBC pts treated with NC and RC between Jan 2005 – April 2013 were evaluated. Standard demographic, disease-related and biochemical parameters (Hb, LDH, albumin) and NLR were analyzed with univariate and multivariable logistic regression. The continuous variable pre-RC NLR was dichotomized using a cut-off of 2.5 based on area under the receiver-operator-curve analysis. Generalized linear mixed model was used to account for the time trend and co-linearity when assessing NLR change between pts who achieved pathological response (pathR) and non-responders. Results: Twenty-three patients were evaluable. Age, gender, ECOG, smoking, clinical stage, and hydronephrosis did not significantly predict for pathR. Pre-NC and mid-NC NLR did not predict for pathR. Pre-RC NLR &lt;2.5 showed a trend towards association with pathR (p=0.05). The pattern of NLR change between responders and non-responders was significantly different (p=0.039). Non-responders exhibited a transient decrease in NLR during NC, followed by an increase in NLR pre-RC above its baseline; responders exhibited a sustained decrease in NLR which remained suppressed until RC (Figure: http://bit.ly/1bYC2wR). Conclusions: While there was no significant difference in pre-NC NLR between responders and non-responders, there was a significant difference in the pattern of NLR change during NC. We speculate that a sustained decrease in inflammatory burden during NC, as manifested by NLR, is associated with pathR. Despite limitations of a small retrospective study, our results may have potential translational and clinical implications.
Phase I study of epirubicin and irinotecan in the second line treatment of extensive stage (ES) small cell lung cancer (SCLC)
Authors: T. Larson, P. Pawloski, D. King
Journal: Journal of Clinical Oncology (2005)

7261 Background: SCLC has high response rates to initial chemotherapy but far fewer patients respond at the time of relapse or with refractory disease to second line therapy. Epirubicin and irinotecan have established roles as single agents in SCLC as well as in combination with other agents but to date, there are no published studies of the two agents used in combination. The purpose of this study was to establish a maximum-tolerated dose (MTD) for the combination and to recommend a phase II dose. Methods: Patients with progressive ES-SCLC and measurable disease following first-line, platinum-based chemotherapy received epirubicin (E) slow IV push over 3–5 minutes followed by irinotecan IV over 90 minutes on day 1 and irinotecan IV over 90 minutes on day 8 every 21 days. The dose levels examined are shown in the table below. Results: Thirty patients are planned for enrollment. To date, 20 patients (9 male/11 female, median age 60; PS 0/1/2 = 2/15/3) meeting the eligibility criteria have been enrolled and treated. Eleven of 20 (55%) patients had refractory (relapse < 3 months of last treatment) disease at study entry. Five of 20 patients have completed six cycles of treatment (25%). One patient is currently receiving treatment. Four of 20 (20%) patients have responded to treatment with a partial response. Ten of 20 (50%) patients have had stable disease (SD) at best response. Five of 20 (25%) patients have progressed after ≤2 cycles of treatment. One patient has experienced a dose-limiting toxicity (DLT) at dose level 4 (neutropenia). Conclusions: The recommended doses for continued phase 2 testing is at least epirubicin 60 mg/m2 IV Day 1 followed by irinotecan 90 mg/m2 IV day 1 and 8 or greater if the remaining 10 patients do not experience dose-limiting toxicities. Activity was seen at all dosage levels. Further study in the phase II setting is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Oncology
Single-institution experience of preoperative chemoradiotherapy for locally advanced gastric cancer.
Authors: J. M. Pepek, J. P. Chino, C. G. Willett, D. S. Tyler, H. E. Uronis, B. G. Czito
Journal: Journal of Clinical Oncology (2011)

99 Background: To examine acute toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer. Methods: Patients with gastroesophageal (GE) junction (Siewert type II and III) or stomach adenocarcinoma who underwent curative intent CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Tumors were staged according to AJCC 6 th edition. Local recurrence was defined as radiographic or biopsy- proven disease within the radiation treatment field. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to CTCAE v4.0. Results: Forty-eight patients (60% stage III, 8% stage IV) were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Thirty-five percent had signet ring histology, 52% had poorly differentiated tumors and 10% had linitis plastica. Median age was 60 years and median RT dose was 45 Gy. All patients received concurrent chemotherapy (CT) with 40 (83%) receiving 5-FU-based CT. Rates of acute &gt; grade 2 hematologic and non-hematologic toxicity were 38% and 10%, respectively. Six patients (13%) required treatment break and two (4%) were unable to complete the prescribed treatment course. Thirty-six patients (75%) underwent surgery. Patients did not undergo surgery due to distant metastases at laparotomy or restaging (n=9), patient refusal (n=2) or poor performance status (n=1). Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS for all patients was 40%. For those undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. Conclusions: Preoperative CRT for gastric cancer is reasonably well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with advanced disease, LC, DFS and OS rates in resected patients are comparable to similarly staged, adjuvantly treated historic controls. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated. No significant financial relationships to disclose.