tbuckley/cabot-search huggingface dataset:
Prognostic factors in patients with WHO grade 3 gliomas: The Cleveland Clinic experience.
Authors: N. Hashemi-Sadraei, H. S. Bawa, A. Satra, G. Rahmathulla, M. Patel, G. Stevens, T. M. Tekautz, L. A. Rybicki, D. M. Peereboom, J. H. Suh, R. Weil, M. A. Vogelbaum, G. Barnett, M. S. Ahluwalia
Journal: Journal of Clinical Oncology (2011)

2053 Background: Anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and anaplastic oligoastrocytoma (AOA) are the major histological categories of WHO grade 3 gliomas. Most randomized trials pool both grades 3 or IV gliomas in their analysis. Consequently, there is limited data on specific prognostic factors for patients (pts) with grade 3 gliomas. Methods: After obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify pts with histologically confirmed grade 3 glioma at the time of diagnosis. Multivariable analysis was conducted with use of a Cox proportional hazards model and a stepwise selection algorithm that used p<.10 as the criteria for entry and p<0.05 as retention in the model to identify independent predictors of survival. Results: Chart records of 336 pts (52% of whom were men) diagnosed between 1994 and 2009 were included for analysis. The median age at presentation was 50 years (range, 1-88 years). 49% of pts had biopsy only, 21% had gross total resection (GTR), 5% had near total resection (NTR), and 25% had subtotal resection (STR). Following surgery, 92% of pts underwent radiation and 62% underwent concurrent chemotherapy. Median overall survival (OS) of AA, AOA, AO was 17.0 months, 58.7 months and 74.2 months respectively. Median OS for all pts was 25.9 months. Five factors were identified as independent predictors of overall survival, age at diagnosis (p<0.001), Karnofsky Performance Status (p<0.001), histology (AA vs. AO, p<0.001), multifocal disease (p=0.012) and type of surgery (GTR vs. biopsy, p<0.001). Conclusions: Older age, poor performance status, AA or AOA histology, and multifocal disease were associated with higher mortality. GTR or STR, relative to biopsy, was associated with lower mortality. Risk factors for mortality: Multivariable Cox proportional hazards analysis Variable Hazard ratio 95% Confidence interval P value Age at diagnosis Per 10-year increase 1.39 1.22-1.58 <0.001 KPS 30-60 vs. 90-100 2.66 1.53-4.62 <0.001 70-80 vs. 90-100 1.99 1.42-2.79 <0.001 Histology Astro vs. oligo 3.28 2.06-5.22 <0.001 Mixed vs. oligo 2.23 1.24-4.04 0.008 Lesion Multifocal vs. unifocal 2.87 1.26-6.58 0.012 Degree of resection GTR vs. biopsy 0.39 0.25-0.63 <0.001 NTR vs. biopsy 0.44 0.19-1.03 0.06 STR vs. biopsy 0.58 0.38-0.90 0.015
Using quality indicators to monitor changes in adherence to clinical practice guidelines for treatment of ductal carcinoma in situ (DCIS) of the breast.
Authors: Laura Chin-Lenn, Lloyd Mack, Walley J. Temple, Peter S. Craighead, Heather E. Bryant, May Lynn Quan
Journal: Journal of Clinical Oncology (2012)

246 Background: Evaluation of the management of DCIS poses challenges, as standard breast cancer outcome measures such as mortality do not apply. Therefore, quality indicators (QIs) were previously developed through an interprovincial, multidisciplinary Delphi process to assess the quality of DCIS treatment and adherence to clinical practice guidelines. Population based treatment of DCIS was then compared over time using these QIs. Methods: Patients diagnosed with DCIS from 2000 to 2001 and 2009 to 2011 were identified on a population basis from the Alberta Cancer Registry and a province-wide prospectively collected synoptic medical report (WebSMR) in Alberta, Canada. Patient charts were reviewed retrospectively and QIs abstracted. Results: A total of 620 patients were identified in the study periods. Results are summarized in the table. In comparison to the earlier group, the recent cohort showed significant improvement in radiation oncology referral, radiation post lumpectomy, and complete pathology reporting. Axillary staging significantly increased from 20% (axillary dissection in 2000 to 2001) to 73% (sentinel node biopsy 2009 to 2011). Other QIs did not differ significantly. Conclusions: Adherence to clinical practice guidelines for DCIS in Alberta measured using developed QIs have shown significant improvements, particularly in pathology reporting, referral to radiation oncologists and uptake of radiation therapy for patients treated with breast conserving surgery. Rates of sentinel node biopsy seem unacceptably high, which requires further investigation. [Table: see text]
A single-arm phase II trial of gemcitabine, oxaliplatin, and panitumumab in KRAS wild-type advanced biliary tract cancer.
Authors: Marcus Smith Noel, Jill N. Allen, Thomas Adam Abrams, Matthew Yurgelun, Jason Edward Faris, Lipika Goyal, Jeffrey W. Clark, Lawrence Scott Blaszkowsky, Janet E. Murphy, Hui Zheng, Alok A. Khorana, Gregory Clayton Connolly, Ollivier Hyrien, Kimmie Ng, Darrell R. Borger, Anthony John Iafrate, Aram F. Hezel, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2014)

255 Background: Biliary Tract Cancer (BTC) encompasses a group of aggressive, genetically heterogeneous tumors with limited systemic treatment options. Currently platinum and gemcitabine-based therapy is the standard first-line treatment. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRASwild-type genetic subtypes of colon cancer. Methods: Patients with histologically confirmed, previously untreated unresectable or metastatic KRAS wild type biliary tract or gallbladder adenocarcinoma with ECOG performance status (PS) 0-2 were eligible. Patients were treated with Panitumumab 6mg/kg, Gemcitabine (GEM) 1000 mg/m 2 (10 mg/m 2 /min), Oxaliplatin (OX) 85 mg/m 2 on days 1 and 15 of each 28 day cycle. The primary objective was to determine the objective response rate (ORR) by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression free survival (PFS), and overall survival. Results: Of the 38 patients screened, 31 patients were found to have KRAS wild type genotype and enrolled. The median age was 61 years old, 55% males, 100% of patients had an ECOG PS of &lt;1. Twenty-five patients had intrahepatic cholangiocarcinoma, and 3 each had extrahepatic and gall bladder carcinoma. Twenty-eight patients completed at least 2 cycles of therapy and were evaluable for response. The ORR was 50% (95% CI 23.8-76.2). With a median follow-up of 11 months, median PFS was 10.5 months (95% CI, 3.8 - 23.9 months) and median OS was 24.8 months (95% CI, 9.0 months-no upper bound). The most common grade 3 toxicities were fatigue 23%, anemia 23%, neuropathy 16%, elevated AST/ALT 16%, hyponatremia 13%, nausea 13%, rash 10%, neutropenia 7%, and hypomagnesemia 7%. Grade 4 toxicities included leukopenia 10%, and 1 case (3%) each of gallbladder perforation, hematoma, anemia, hyperkalemia, hyponatremia and hypokalemia. Conclusions: Completed analysis of this phase II study of GEMOX-panitumumab for KRAS wild type advanced BTC reveals encouraging results with promising response rates and PFS. The toxicity profiles were expected and manageable. Further investigation of this regimen and anti-EGFR therapy is warranted. Clinical trial information: NCT01308840.
Promoting a Culture of Safety as a Patient Safety Strategy
Authors: Sallie J. Weaver, Lisa H. Lubomksi, Renee F. Wilson, Elizabeth R. Pfoh, Kathryn A. Martinez, Sydney M. Dy
Journal: Annals of Internal Medicine (2013)

Developing a culture of safety is a core element of many efforts to improve patient safety and care quality. This systematic review identifies and assesses interventions used to promote safety cult...
Long-term results from EORTC24971/TAX323: Comparing TPF to PF in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN).
Authors: J. B. Vermorken, E. Remenar, C. Van Herpen, M. Degardin, J. S. Stewart, R. Karra Gurunath, C. Fortpied
Journal: Journal of Clinical Oncology (2011)

5530 Background: At a median follow-up (FU) of 32.5 months, the original EORTC24971/TAX323 study showed that compared with standard cisplatin/infusional fluorouracil (PF), induction chemotherapy (ICT) with the addition of docetaxel (TPF) prior to radiotherapy significantly improved progression-free survival (PFS) and overall survival (OS) with less toxicity and an improved quality of life in patients with unresectable SCCHN (NEJM 2007; 357: 1695; BJC 2010; 103: 1173). The present report describes survival data after a median FU of 8.6 years and long-term side effects (feeding tube dependency, tracheostomy, gastrostomy and second malignancies). Methods: Data were collected in a long-term FU form and analyzed in the intent-to-treatment population, using a Cox PH model adjusted for treatment, tumor site, T&N stage and performance status. The two treatment arms were also compared with an unstratified logrank test at a 2-sided 5% significance level. The clinical database was locked on January 10, 2011. Results: FU forms were obtained from 308 (86%) of the 358 randomized patients (156 TPF, 152 PF). PFS remained significantly better with TPF compared with PF (hazard ratio [HR] unadjusted 0.71 (95% CI, 0.57-0.89), p=0.003, medians of 12.7 vs 8.6 months, and 5-years PFS 22.9% vs 13.5%, mainly due to less locoregional progression). A similar picture was observed for OS (HR unadjusted 0.74 (95% CI, 0.59-0.94), p=0.011, medians of 18.8 vs 14.5 months, 5-years OS 27.5 vs 18.6%). These data were confirmed in the Cox PH model. Long-term side effects in TPF/ PF arms were: tracheostomy 13/9 ; feeding tube dependency 6/10; gastrostomy 19/19; second malignancy 14/6 (of which lung 42.9%/50%; H&N 42.9%/33.3%, and GI 14.3%/16.7%). Conclusions: This long-term update supports the conclusions of the final analysis that TPF is superior to PF as ICT for patients with unresectable SCCHN.
The breast cancer lifestyle intervention study.
Authors: Jennifer Chun, Erica Brooke Friedman, Freya Ruth Schnabel, Martha Eddy, Shira Schwartz, Elizabeth Kern, Deirdre Kiely, Amber Guth, Deborah M. Axelrod
Journal: Journal of Clinical Oncology (2013)

112 Background: Maintaining a healthy weight after breast cancer diagnosis has been associated with improved survival outcomes. Lifestyle interventions are particularly important in overweight women who are at an increased risk of overall and breast-cancer specific death compared to non-overweight women. The purpose of this study is to examine the barriers and acceptance of a lifestyle intervention program among overweight women with newly diagnosed breast cancer. Methods: The Breast Cancer Database of NYU Langone Medical Center was queried for women who were newly diagnosed with breast cancer and who had a body mass index (BMI) ≥25kg/m 2 . Eligible patients participated in the Moving for Life (MFL) exercise program for 16 sessions. Questionnaires were administered at baseline and at the end of the intervention. Descriptive statistics were used to summarize patient characteristics and paired t-tests were used to see if there were any significant differences before and after the intervention. Results: A total of 40 women were eligible to participate in the MFL exercise program. A total of 20 women declined to participate due to location, transportation limitations, and conflicts in schedule. Of the 18 women who enrolled in the MFL program, 13 (72%) were regular attendees and completed the study. The median age was 61 years (range: 38-76) and the average baseline BMI was 31kg/m 2 (range: 25-42). After completing the MFL intervention, there was a significant decrease in weight and BMI (p=0.04). The average weight loss was 10lbs. Participants also reported a greater enjoyment of exercise (p=0.02), as well as a decrease in pain related to treatment (p=0.05). Conclusions: Moving for Life is a unique exercise program for breast cancer patients and had a high rate of acceptance and completion in a cohort of overweight breast cancer patients. This study resulted in a statistically significant average weight loss of 10lbs, as well as a greater enjoyment of exercise and decrease in treatment-related pain which may impact long-term lifestyle changes. Longitudinal follow-up at 6- and 12-months will allow assessment of secondary endpoints, including exercise frequency and attitudes about exercise, allowing us to examine sustainability and changes in behaviors and attitudes over time.
My choices, my wishes: Advance care planning advocacy in the adult oncology population.
Authors: Sabrina Q. Mikan, J. Russell Hoverman, Debra A. Patt, Brian Turnwald
Journal: Journal of Clinical Oncology (2012)

6 Background: Working through end-of-life care (EOL) issues with our patients is one of the most challenging aspects of cancer care. Although studies of EOL care interventions that are patient-focused and result in high-quality EOL experiences are increasing, most still do not achieve an EOL experience consistent with preferences. We aimed to provide an intervention for standardized advanced care planning (ACP) documentation and education to improve quality of life (QOL) for patients (pts) with terminal cancer (TC). Methods: Pts with TC (for this study defined as stage IV cancer or metastatic disease) were evaluated retrospectively through our EHR IKnowMed (IKM) before and after an ACP documentation and an education intervention. Descriptive statistics were used to identify and measure utilization of ACP introduction and charting as well as completion of advance directive documentation. Within IKM there are discrete fields for EOL data including ACP discussion, ACP facilitation, documentation of ADs. Education on tool documentation occurred in early 2012. Our ACP program was launched in March 2012. This included an ACP office visit conducted by a practitioner with ACP training, standardized education literature on EOL and ACP, launch of a website with EOL and ACP educational material, recording of ACP documents and documentation of hospice utilization and ACP preferences within our EHR. Results: Baseline characteristics and improvements in ACP introduction, charting, and AD documentation that occurred during our documentation and intervention process can be seen in the Table. Conclusions: Implementation of a standardized ACP program improves utilization and documentation of ACP planning, and documentation of ADs. These interventions improve QOL and health literacy for patients with TC. By incorporating these strategies with definable metrics, strategic intervention can be measured and reported. Further study of the relationships between ACP documentation and patient outcomes is necessary for comprehensive oncology care. [Table: see text]
Utility of a three-dimensional bioabsorbable tissue marker in delineating the lumpectomy cavity.
Authors: Michael Cross, Joe Ross, Scott Jones, Thad Beck
Journal: Journal of Clinical Oncology (2013)

78 Background: Advanced methods of external beam radiotherapy are not widely used to deliver post-operative treatment for breast cancer due to difficulty in defining the target region surrounding the surgical cavity. Common targeting methods utilize surgical clips and/or seroma based tissue changes. However, these methods can result in over-estimation of treatment volumes resulting in undesirable radiation exposure to adjacent normal tissues. In addition, these techniques fall short of the required precision necessary to utilize newer methods of radiation delivery. In order to assess its ability to assist with identification of the surgical excision site, we evaluated a 3-dimensional tissue marker surgically placed during partial mastectomy. Methods: A total of 30 patients were implanted with a 3-D bioabsorbable tissue marker at the time of partial mastectomy. Post-operative CT simulation and treatment plans were generated and compared. The tissue marker was rated for its utility in defining the target area for treatment planning as well as day to day patient positioning between fractions. Most patients received standard whole breast irradiation with a boost to the tumor bed as treatment, however advanced techniques were used in selected cases. Results: The marker was easy to use with standard surgical techniques. No complications were reported and it was consistently and easily visualized with clinical imaging allowing it to be readily incorporated into standard and advanced planning methods. The marker had appreciable benefits when designing optimal treatment plans, particularly when no seroma fluid remained. In these cases, the marker identified the surgical site that could not have been identified using traditional methods, and target volumes were decreased by &gt;40% in most cases. In addition, the device assisted with image-based tracking of the lumpectomy cavity during respiratory motion (4-D CT) enabling use of IGRT. Conclusions: The Biozorb tissue marker provided a consistent method for identifying the lumpectomy site and was a useful tool for post-operative radiotherapy and clinical followup. In addition, it provided a novel method of marking the lumpectomy cavity when using oncoplastic techniques.
Src inhibition through a phase II study of 5-fluorouracil, oxaliplatin, plus dasatinib (FOLFOX-D) in first-line metastatic pancreatic adenocarcinoma.
Authors: Thomas J. George, Alison Marguerite Ivey, Karen Colleen Daily, Long H. Dang, Scott Watson, Renee Granicz, Kevin Tormes, Xiaomin Lu, Chen Liu, Carmen Joseph Allegra, Kevin Behrns, Steven J. Hughes, Olorunseun Olatunji Ogunwobi, Jose Gilberto Trevino
Journal: Journal of Clinical Oncology (2014)

319 Background: Triplet drug therapy is now a standard for metastatic pancreatic cancer (mPCa) but limited in use due to toxicity. Src is constitutively active in mPCa and associated with increased chemoresistance. Src inhibition increases oxaliplatin (ox) activity. Inhibition of Src reduces tumor expression of thymidylate synthase with subsequent 5FU chemoresistance reversal. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) capable of inhibiting Src. Demonstrating activity of this triplet combination therapy in mPCa represents a scientifically rational approach to a clinical unmet need. Methods: Eligible pts have biopsy proven, RECIST measurable disease with no prior therapy for met disease and at least 6 months since completing adjuvant therapy, ECOG PS 0-2 and adequate organ function. Pts received standard doses of mFOLFOX6 chemotherapy (5-FU/LV 400mg/m 2 bolus and Ox 85 mg/m 2 D1; 5-FU 2,400 mg/m 2 CIVI x 46h D1-2) with continuous D (150 mg PO daily) repeated q14d with tumor assessments q8w. The primary endpoint is progression-free survival (PFS) with secondary endpoints of objective and biochemical response rates, freedom from mets, overall survival (OS), toxicity, and quality of life. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months (m). Results: 14 of 42 planned pts have received therapy and are included in this report. Baseline pt demographics are in the table. 10 pts (71%) had a grade 3 AE and 1 (7%; sepsis) had a grade 4 AE. There were no grade 5 toxicities. Most common grade 3 AEs included anemia (29%), hyponatremia (29%), neutropenia (21%) and fatigue (21%). Conclusions: Enrollment continues with ongoing toxicity and efficacy monitoring of this targeted combination. Exploratory tissue and serum correlative analyses to identify predictors of response are planned. Clinical trial information: NCT01652976. [Table: see text]
Clinical and molecular assessment of response to regorafenib.
Authors: Nao Kakizawa, Koichi Suzuki, Yuji Takayama, Kosuke Ichida, Taro Fukui, Fumiaki Watanabe
Journal: Journal of Clinical Oncology (2016)

568 Background: Regorafenib provides anti-tumor effects in 3rd or 4th line for metastatic colorectal cancer patients (pts), but some of pts show severe adverse effects (AE). It is, therefore, crucial to select patients more likely benefit from regorafenib. Methods: Twenty pts were treated with regorafenib for metastatic colorectal cancer and 91 plasma samples from 16 pts were available for monitoring of circulating tumor DNA (ctDNA) in blood. The treatment response, adverse effects, progression-free survival (PFS), overall survival (OS) and morphologic response in CT image were evaluated. KRAS mutant ctDNA (MctDNA) was determined by digital PCR. Results: According to Response Evaluation Criteria in the Solid tumors (RECIST), 6 patients (30%) showed SD, and 8 pts (40%) exhibited PD. Median PFS was 1.2 months (range; 0.2-14.2 months), and median OS was10.6 months (range; 0.7-15.6 months). Treatments are continued for 4 pts but discontinued for others. The reasons of discontinuation were PD for 8 pts and AE for 7 pts. Seven pts showing AE include 3 pts with liver function disorder, 3 pts with severe fatigue and one pt with Grade 3 skin toxicity. Three pts with liver function disorder showed extensive multiple liver tumors. PS 2 was seen in 2 pts with severe fatigue. PFS in pts showing treatment discontinuation due to AE was 0.6 month but PFS in pts with other reasons rather than AE was 3.3 months. According to morphologic response criteria, 3 among 6 pts harboring SD in RECIST, showed optimal response in early period of the treatment. These 3 pts with morphological response showed better PFS such as 3.5, 5.3, and 14.2 months, respectively. Six pts displayed KRAS mutant ctDNA (MctDNA) in blood. Among them, 2 pts showed MctDNA during treatment and then exhibited tumor progression. Emergence of MctDNA was observed in one pt without KRAS mutation in tumor tissues. MctDNA was detectable in the blood of these 2 pts prior to radiographic detection of disease progression. Conclusions: Pts with extensive multiple liver tumor or poor PS unlikely benefit from Regorafenib. Pts with optimal morphologic response likely benefit from Regorafenib by adequate management of other AEs. In addition, monitoring of KRAS mutation in ctDNA could be predictive biomarker for treatment response.