tbuckley/cabot-search huggingface dataset:
Updated response and survival data for TNFerade combined with chemoradiation in the treatment of locally advanced pancreatic cancer (LAPC)
Authors: N. Senzer, N. Hanna, T. Chung, J. Nemunaitis, A. Rosemurgy, M. Javle, T. Reid, M. Posner, K. J. Chang, J. R. Hecht
Journal: Journal of Clinical Oncology (2005)

4097 Background: TNFerade is a replication-deficient adenovector containing the human TNF-α gene regulated by a chemoradiation-inducible promoter, Egr-1. This dose-selection component of a phase II study evaluated the safety and early efficacy of TNFerade + chemoradiation in patients with LAPC. Methods: Standard sequential dose-escalating design was used. Five-week treatment consisted of weekly intratumoral injections of 4 x 109, 4 x 1010, 4 x 1011 or 1 x 1012 pu TNFerade, continuous infusion 5-FU (200 mg/m2/day x 5 days/wk) and 50.4 Gy radiation (1.8 Gy fractions). TNFerade was administered by image-guided percutaneous transabdominal approach (PTA) or via an ultrasound-guided endoscopic approach (EUS), based on site preference. Endpoints: Safety, radiographic tumor response, time to progression, CA 19–9 and survival. A standardized spiral CT protocol was used and an independent core lab assessed responses. Results: Dose-escalation is complete with 50 patients enrolled. Dose-limiting toxcities (DLTs) occurred in a PTA patient at 4x1010 pu (hypotension, grade 3), and in three EUS patients at 1x1012 pu (recurrent pancreatitis, pancreatitis, and billiary obstruction), setting the maximally tolerated dose (MTD) at 4x1011 pu for this protocol. All non-DLTs potentially related to TNFerade were grade 1–2, and primarily included fever (28%), rigors (20%), and fatigue (16%). Serum TNF-αmax was 129 pg/ml. Compared with the first two cohorts (n=30), the 4x1011 pu dose (n=7) was associated with greater (100%) locoregional control of treated tumors at 3 months post-treatment, longer survival without progression, a greater proportion of patients with stable or decreasing CA 19–9, a greater percentage of patients resected, and improved overall survival (median survival not yet reached at a minimum follow-up of 16 months). Data for the 1x1012 pu cohort (n=9) is under analysis, and the 4x1011 pu cohort has been expanded (n=4). Conclusions: TNFerade combined with chemotherapy shows promise in treatment of LAPC. A dose of 4x1011 pu TNFerade is generally well tolerated and is the proposed dose for the randomized phase of this study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GenVec
A feasibility study of an aromatase inhibitor (AI), letrozole (L) and the antibody to vascular endothelial growth factor (VEGF), bevacizumab (B), in patients (pts) with hormone receptor-positive metastatic breast cancer (MBC)
Authors: T. A. Traina, M. N. Dickler, J. F. Caravelli, B. M. Yeh, E. Brogi, K. Panageas, S. A. Flores, L. Norton, C. Hudis, H. Rugo
Journal: Journal of Clinical Oncology (2005)

796 Background: In DMBA-induced animal models of breast cancer, estrogen (E) induced expression of VEGF whereas AI therapy (Rx) had the opposite effect (Nakamura, 1996). We hypothesize that E-induced VEGF expression supports breast tumor growth, therefore E reduction using an AI with B could be superior in activity to either agent alone. This study explores the feasibility of letrozole + bevacizumab in MBC. Methods: Eligible pts have MBC and are candidates for AI Rx. Prior non-steroidal AI use without progression is permitted. Rx consists of letrozole (2.5 mg daily) and bevacizumab (15 mg/kg IV q3 weeks). Premenopausal pts are rendered menopausal. Primary endpoint is toxicity; secondary endpoints include response rate, clinical benefit rate and time to tumor progression. Using a two-stage design, 19 pts will be accrued to the first stage. If ≤ 2 pts have grade (gr) 4 toxicity (excluding venous thrombosis), then 23 pts will be added. If ≤ 4/42 pts have gr 4 toxicity, the regimen is feasible. Markers of the ER, HER2 and VEGF pathways will be evaluated in archival tumor tissue. Serial levels of circulating endothelial cells and epithelial cells as well as plasma VEGF and bFGF will be measured. Results: The trial was activated 8/24/04. As of 12/2/04, eight pts have been enrolled: median age 50 (range 36–59); ECOG 0 (0–1); sites of MBC: bone only 5/8; liver 3/8; ER+/PR+ 8/8; HER2+ 0/8. Prior adjuvant Rx: chemotx (CRx) 6/8, tamoxifen 5/8. MBC Rx: CRx 0/8, first-line letrozole 8/8 started at median of 37.5 wks (3–118) before B. Median 2 cycles/pt (range 1–4+). Toxicity: gr 2 hyperglycemia 1/8, gr 2 leukopenia 1/8; no gr 3–5 toxicity. All pts are too early for response assessment. Endothelial and epithelial cells are measurable in all patients. Conclusions: Combination letrozole and bevacizumab appears well tolerated. Accrual continues and updated safety and efficacy data is anticipated. Supported in part by Genentech, Inc. and Novartis Pharmaceuticals. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Genentech Genentech and Novartis to MSKCC and UCSF
The value of a genetic counselor for patient identification.
Authors: Jennifer N. Eichmeyer, Dan Sayam Zuckerman, Thomas M. Beck, Nicolas Camilo, Patty Sproat, Christa Burnham
Journal: Journal of Clinical Oncology (2012)

97 Background: Advances in genetics are rapidly changing cancer care and requiring institutions to maximize the unique skills of genetics professionals. The identification of genetic syndromes is vital for prevention and management of families with high cancer risks. Despite this high risk patients and families who qualify for genetic counseling are not referred; this is due to increasing responsibilities on physicians. Genetic counselors could be utilized to review new oncology charts to improve identification. Methods: A genetics assessment tool developed by NCI Community Cancer Centers Program generated baseline measurements of 2010 tumor registry data of patients meeting NCCN guidelines for genetics evaluation. A weekly list of new oncology patients was provided to a genetic counselor who reviewed each H&amp;P dictation focusing on the pathology, age, and family history sections. The genetic counselor notified the oncologist by email or through the EMR system, and the physician discussed genetic counseling with patient or approved the order. Post implementation of the chart review program was measured using 2011 tumor registry data. Results: In 2010 58% of total applicable patients were offered a genetics evaluation. In 2011 this improved to 70%. Based on disease type: 69% (breast), 59% (colon), 29% (ovary), and 20% (uterine) were offered a genetics evaluation in 2010. In 2011 these numbers were 76% (breast), 64% (colon), 91% (ovary), and 20% (uterine). Over a 10-month period a total of 122 patients were identified through the chart review program by the genetic counselor. Three of these were confirmed to have a genetic mutation for one of the hereditary cancer syndromes. An average week included review of 73 charts for 10 medical oncologists, 4 radiation oncologists, 4 pediatric oncologists, which generated 60 to 80 minutes of work weekly for the counselor. Conclusions: This program improved patient identification and allowed physicians to become more aware of opportunities for genetic consultation that led to a streamlined referral process and allowed more applicable patients to receive counseling and testing. Project funded in whole or part with Federal Funds from the National Cancer Institute, National Institutes of Health, Contract No. HHSN261200800001E.
A quality improvement program to increase performance with clinical oncology pathways.
Authors: Janet L. Espirito, Aimee Arlen, Jody S. Garey, Sheetal Sheth, Brian Turnwald, Matthew Clayton, Jennifer Flinn, Carla Butler-Dorian, Greg C. Nelson, J. Russell Hoverman, Debra A. Patt, Thomas H. Cartwright, Leslie T. Busby, Roy A. Beveridge, Marcus A. Neubauer
Journal: Journal of Clinical Oncology (2012)

65 Background: Several organizations have created oncology pathways (pws) to support evidence-based medicine, and both standardize and improve the quality of care. Information is scarce; however, regarding the requirements for successful implementation of a pws program and monitoring of adherence. Methods: We assessed the efficacy of a quality assurance initiative called Practice Pathways Improvement (PPI) program to increase pws adherence to The US Oncology Network’s physician-developed Level I Pathways. We queried our electronic health record (EHR) iKnowMed to collect data before and after program initiation. Education was provided to address policies and procedures; leadership roles and responsibilities; integration of pws into the EHR and workflow; and the importance of correct data entry into the EHR. We then measured metrics including levels of assessable data (AD) (complete data, no missing or conflicting elements); On-Pathway adherence (ON-PW); and documented rationale for exceptions (EX) of Off-Pathway treatments. Metric performance reports were distributed monthly. Results: Since 2010, 10 practices of varying size (6-342 medical oncologists) and sites (2-47) voluntarily participated. Program duration ranged from 6-12 months (mos). There were 42,266 regimens evaluated during the program, covering 19 disease pws. Baseline averages, results at program end, and current averages (avg) for AD, ON-PW, and EX are shown in the Table. As of June 2012, average follow up was 19 mos (range 13-25). A normal approximation shows significance of p &lt; 0.001. Conclusions: Implementation of a quality assurance initiative containing operational, leadership, and workflow elements along with continued education is important for successful pws adherence. Tailored program components are necessary to meet individual practice needs. Establishing a foundation for a pws process is important to maintain performance over time. As the reimbursement landscape in oncology evolves, the ability to demonstrate quality of care is essential. [Table: see text]
Recruitment in the Internet era: An efficient strategy for a study of breast cancer risk.
Authors: L. M. Yackowski, F. R. Schnabel, R. Oratz, D. Roses, R. Wieder, C. Kowalczyk, H. Ostrer
Journal: Journal of Clinical Oncology (2011)

1531 Background: The NYU Jewish Women’s Breast and Ovarian Cancer Genetics Study (JWBOCGS) employed 3 recruitment strategies to develop a large cohort of Ashkenazi Jewish (AJ) women for a breast cancer genome-wide association study. Two successful studies of cancer risk in the AJ population serve as historical comparisons ( Struewing JP et al. 1997.NEJM 336:1401-1408; King MC et al. 2003. Science 302:643-646). Methods: The recruitment modalities include clinic-based enrollment, community outreach events, and Internet-based self-identification through the Avon/Love Army of Women (AOW). Enrollment involves completing a questionnaire and providing a saliva sample. AOW recruitment was launched nationally by e-blast on November 10, 2010. The recruitment strategies were compared by subjects enrolled, number of recruitment sites, and time. Results: The table summarizes the recruitment yields. As of February 1, 2011, 3145 AJ women responded to the AOW e-blast, 2,768 (88.0%) completed the online eligibility survey, 1,396 (50.4%) are eligible, and 271 completed enrollment within the first 11 weeks. Conclusions: Internet-based recruitment through AOW is an efficient strategy regarding time and number of recruitment sites. This effort has also been less cumbersome than traditional methods employed in this and other studies. Utilization of AOW expanded the reach of this study to a national level. Recruitment summary. Study Eligibility Strategy No. of sites/events No. of subjects Time JWBOCGS AJ women: High risk family or low risk > 60 y.o. Clinic 4 sites 506 8/08-12/10 (28 mo.) Outreach 19 educational events 3 conference exhibits 223 1/09-5/10 (17 mo.) AOW 1 site 271 11/10-2/11 (11 wks.) Struewing et al. AJ men and women > 20 y.o. Posters, media announcements 15 sites 5,318 Prior to 5/97 (9 wks.) King et al. AJ patients with breast cancer Clinic 12 sites 1,008 9/96-12/00 (51 mo.)
Are there survival benefits in portal vein resection for pancreatic cancer?
Authors: W. Lou, D. Wang, D. Jin
Journal: Journal of Clinical Oncology (2008)

15646 Background: The outcome after pancreatic resection with en bloc portal vein resection for pancreatic cancer has not been fully clarified Methods: The pathological and survival relationship of fifteen patients who accepted en bloc pancreatic and portal vein resection was retrospectively investigated. Results: Fifteen patients with pancreatic cancer underwent pancreatectomy portal vein resection from January 2002 to December 2005. Histological examination revealed that 7 patients had definite tumor invasion of the intima of the portal vein (Group I). In the other 8 patients, the intima had not been invaded (Group II). The median survivals of the Group I and II were 8.7 and 15.9 months respectively. There was a significant difference in survival rates (P=0.001) between the patients with and without tumor invasion of the intima. Conclusions: Patients without tumor invasion of the intima achieved improved survival after en bloc pancreatic and portal vein resection. No significant financial relationships to disclose.
Colorectal treatment effectiveness in a population-based registry: A 1991-1994 and 2001-2005 comparison.
Authors: Ge Lin
Journal: Journal of Clinical Oncology (2012)

647 Background: Providing state and regional cancer treatment prognoses, and comparing them over time are important for both local patients and physicians. The present study is the first in Nebraska, US to compare the change in prognostic factors for five-year survival of CC patients to those of RC patients from two time periods, 1991-1994 to 2001-2005. Methods: CC and RC Patients aged 19 years and older were selected from the Nebraska Cancer Registry the two time periods. The outcome variable was five-year survival (survived or not) from the date of diagnosis up to five years or more. Treatment was divided into five groups: surgery alone, surgery with chemotherapy and radiation therapy (S+CT+RT), surgery with chemotherapy (S+CT), other treatments, and no treatment. Multivariate logistic regression analysis was used to examine the effect of prognostic factors on five-year survival. Results: There was a 7% five-year survival improvement in RC patients from time 1 to time 2 but no survival improvement in CC patients. Younger age, female, being married, and early stage at diagnosis were associated with CC survival advantage in time 1 and time 2. In contrast, for RC patients, female had no survival advantage in time 2 while those in the 65-74 age group showed improved survival with time. With regard to treatment, surgery alone was the most consistent prognostic factor through time, while S+ CT+RT became the most important prognostic factor for survival in RC in time 2, and S+CT became the most important prognostic factor for survival in CC in time 2. Conclusions: There was marked change in treatment modalities for both CC and RC patients between the 1991-1995 and 2001-2005 periods, with a general trend toward better five-year survival prognosis. The most effective treatments for CC and RC patients in the most recent period are Surg+CT and S+CT+RT, respectively.
Molecular epidemiology of RAS/RAF-mutant colorectal cancer metastases.
Authors: Chloe Evelyn Atreya, James Watters, Steve Rowley, Joon Sang Lee, Oleg Iartchouk, Madelyn Light, Robert S. Warren, Alan Paul Venook
Journal: Journal of Clinical Oncology (2014)

470 Background: A comprehensive molecular characterization of primary colorectal cancers (CRC) was recently reported. Less is known about mutation patterns in CRC metastases and association with survival. Our sequencing analysis focused on CRC liver metastases with RAS/RAF mutations, representing a patient population with limited therapeutic options. Methods: DNA was extracted from formalin-fixed paraffin-embedded CRC liver metastases. Fifty tumors found by Sequenom MassARRAY to harbor KRAS, NRAS or BRAF mutations underwent next generation sequencing on the Ion AmpliSeq Comprehensive Cancer Panel of 409 genes. Co-investigators were blinded to Sequenom mutations identified at UCSF. Variants called by Strelka and VarScan were extensively filtered to control the False Positive Rate and find mutations occurring with &gt; 5-10% variant allele frequency compared to normals. The dataset was evaluated for significant co-mutations, biclustering, and population probabilities of mutations. Results: Following sequencing, 37,744 variants were called in 409 genes with a median coverage depth of 1053x. After filtering to minimize false positives, 2335 variants in 315 genes remained. ARID1A and PIK3R1 were the most significantly associated co-mutation pair, P &lt; 3.5e -5 . Biclustering showed no stratification of patients; genes stratified only by mutation frequency. Further filtering yielded 1,186 variants present at &lt; 1% allele frequency within 1,000 Genomes, of which 131 variants in 24 genes are referenced in the Catalog of Somatic Mutations in Cancer. In addition to anticipated mutations in mismatch repair genes and the RTK/RAS/PI3K, Wnt, TP53, and TGF beta pathways, infrequent mutations were found in Akt1, mTOR, MET and PPP2R1a. After APC, TP53 was the most commonly mutated gene, in 44% of the tumors (95% cl: 31.1% - 57.8%). Survival was similar with mutation of RAS/RAF plus either TP53 or PIK3CA. Conclusions: Next generation sequencing was used to characterize co-variants in RAS/RAF mutated CRC liver metastases. The complexity of our results is consistent with the clinical observation that targeting RAS/RAF mutated metastatic CRC is a formidable challenge. These analyses may nonetheless inform the design of future clinical trials.
Locally advanced rectal cancer (LARC): A 12-year experience of multimodality approach.
Authors: F. Bertolini, L. Scarabelli, C. Del Giovane, S. Zironi, G. De Marco, A. Fontana, R. Depenni, F. Bertoni, G. Luppi, P. F. Conte
Journal: Journal of Clinical Oncology (2011)

607 Background: Main objective of the report is to review retrospectively a 12 years experience of pre-operative chemo-radiotherapy (CRT) in patients (pts) with LARC at the University Hospital of Modena and to correlate clinical variables with outcome. Methods: Between 1998 and 2010, 275 consecutive pts with stage II, III and IV (oligometastatic in lung or liver) LARC who underwent neo-adjuvant CTR were identified from a single institution. All pts received fluoropyrimidine-based chemotherapy (alone or in combination) and RT (50-50.4 Gy). Results: On 275 pts, 166 were males (61%) and 109 females (39%); median age: 65.9 years (range: 26-84). Rectal primary site (on 260 pts): 112 low (43%), 91 medium (35%) and 57 high (22%). Stage at diagnosis (on 245): 2 cT2N0 (0.8%), 8 cT2N+ (3.3%), 68 cT3N0 (27.8%), 134 cT3N1 (54.7%), 11 cT4N0 (4.5%), 22 cT4N1 (8.9%). Pre-operative treatment (on 268 pts): 168 pts (62.6%) received 5fluorouracil (5FU) in continuous infusion, 37 (13.9%) capecitabine, 36 (13.5%) FU+oxaliplatin and 27 (10%) 5FU+cetuximab (clinical trial). On evaluable 177 pts, only 25 (14%) developed G3 toxicity and subsequent treatment interruption. No grade 4 toxicity was recorded. 252 pts underwent surgery (18 pts are still ongoing; 5 did not receive surgery for multiple distant metastases at pre-operative staging): 189 anterior resection (75%), 59 abdominal-perineal amputation (23.4%) and 4 endoscopic resection (1.6%). On 235 pts, 148 obtained a T and/or N downstaging (63%). Dworak tumor regression grade (TRG) was (on 209 pts): TRG4 (pathological complete response) 38 (18.3%), TRG3 37 (17.8%), TRG2 67 (32%), TRG1 63 (30%) and TRG0 4 (1.9%). 5 y-disease free survival (DFS) and overall survival (OS) are 75% and 73%, respectively. Down-staging, TRG 3-4 and histological features like the positivity for radial margins and vascular invasion correlate with both DFS and OS. Conclusions: Pre-operative CRT is well tolerated; downstaging, TRG and histological features such as radial margins and vascular invasion are the strongest predictors of survival. No significant financial relationships to disclose.
The role of salvage extended lymph node dissection (LND) in patients with rising PSA and PET/CT scan detected nodal recurrence of prostate cancer.
Authors: Daniel Porres, Daniar Osmonov, Alexey Aksenov, Andrea Katharina Thissen, Timur H. Kuru, David J. K. P. Pfister, Klaus-Peter Junemann, Axel Heidenreich
Journal: Journal of Clinical Oncology (2016)

242 Background: According to the risk constellation recurrence rate of prostate cancer following local therapy is up to 60%. Early salvage radiotherapy already showed a benefit in progression-free survival. We analyzed the impact of salvage extended lymph node dissection on cancer control in patients with rising PSA and nodal recurrence in PET/CT scan. Methods: Between 2003 and 2015 we performed a salvage extended lymph node dissection in 95 patients with rising PSA and nodal recurrence in PET/CT scan after previous local therapy for prostate cancer. The extent of resection field was adjusted to the pre-operative imaging. Results: We identified 95 patients with rising PSA and nodal recurrence in PET/CT scan with a mean age of 66 years (55-76 years). There were no significant intraoperative complications. Postoperatively, 12% had Clavien/Dindo grade 3 complications. Complete PSA response, defined as a postoperative PSA level &lt; 0.2 ng/ml, was diagnosed in 36% of patients. With a median follow-up of 19 months (1-101 months) cancer-specific mortality rate was less than 1%. Median progression-free survival was 7 months (1-43 months). The interval until the initiation of systemic treatment was 12 months (1-43 months). Conclusions: Salvage LND can be performed without significant complications. Immediate complete PSA response can be achieved in one third of patients and systemic therapy can be delayed by one year. For a general treatment recommendation individual predictive markers are currently still missing.