tbuckley/cabot-search huggingface dataset:
Genetic alterations in esophageal cancers: Detection by next-generation sequencing and potential for therapeutic targets.
Authors: Victoria Meucci Villaflor, Deric Wheeler, Mari Iida, Smruti Vidwans, Michelle Turski, Toni M Brand, Brian Won, Mark K. Ferguson, Marco G. Patti, Mitchell Posner, Irving Waxman, Gavin Gordon, Everett E. Vokes, Ravi Salgia
Journal: Journal of Clinical Oncology (2014)

e22065 Background: A large number of esophageal cancer patients present with advanced or metastatic disease and their overall prognosis is poor. In order to improve survival, we need to identify molecular abnormalities and apply novel targeted therapies. Methods: In order to characterize esophageal cancers (adenocarcinoma (AC) and squamous cell carcinoma [SCC]), we systematically obtained next generation sequencing (NGS) data through established platforms on tumors from patients with esophageal cancer. Patients were enrolled on an IRB approved protocol, and had tissue banked for molecular testing. Clinical characteristics of the patients were also evaluated. Results: Our initial cohort comprised 4 SCC and 16 AC patients. Of AC patients, 14 were male, 11 had a history of tobacco use and 4 had Barrett’s esophagus. Of patients with SCC, all 4 were female and 3 had a history of tobacco use. We found that each patient's tumor DNA analysis had a unique mutational profile. As expected, p53 mutations were extremely common (90% of patients). Interestingly, we identified cyclin pathway aberrations in 75% of these tumors. In addition, the FGF ligand and its receptor (FGFR) were amplified or mutated in 20% of patients tested. The MET/HGF pathway was also noted to be aberrant in 2 esophageal cancer samples. Utilizing the genetic information, we have identified unique sets of alterations and the FGF pathway stands out. We have linked the various genetic abnormalities with potential targeted therapies and active trials are now open. Conclusions: Based on the NGS information from these esophageal tumors, we have been able to identify potential drug targets and therapeutic trials that are available. It is important to study each individual tumor in order to design targeted therapeutic approaches.
Expression of Neuroendocrine Factor VGF in Lung Cancer Cells Confers Resistance to EGFR Kinase Inhibitors and Triggers Epithelial-to-Mesenchymal Transition
Authors: Wen Hwang, Yu-Fan Chiu, Ming-Han Kuo, Kuan-Lin Lee, An-Chun Lee, Chia-Cherng Yu, Junn-Liang Chang, Wen-Chien Huang, Shih-Hsin Hsiao, Sey-En Lin, Yu-Ting Chou
Journal: Cancer Research (2017)

Mutations in EGFR drive tumor growth but render tumor cells sensitive to treatment with EGFR tyrosine kinase inhibitors (TKI). Phenotypic alteration in epithelial-to-mesenchymal transition (EMT) has been linked to the TKI resistance in lung adenocarcinoma. However, the mechanism underlying this resistance remains unclear. Here we report that high expression of a neuroendocrine factor termed VGF induces the transcription factor TWIST1 to facilitate TKI resistance, EMT, and cancer dissemination in a subset of lung adenocarcinoma cells. VGF silencing resensitized EGFR-mutated lung adenocarcinoma cells to TKI. Conversely, overexpression of VGF in sensitive cells conferred resistance to TKIs and induced EMT, increasing migratory and invasive behaviors. Correlation analysis revealed a significant association of VGF expression with advanced tumor grade and poor survival in patients with lung adenocarcinoma. In a mouse xenograft model of lung adenocarcinoma, suppressing VGF expression was sufficient to attenuate tumor growth. Overall, our findings show how VGF can confer TKI resistance and trigger EMT, suggesting its potential utility as a biomarker and therapeutic target in lung adenocarcinoma. Cancer Res; 77(11); 3013-26. ©2017 AACR.
No news, bad news? A deeper examination of the correlation between patient functional status and level of postoperative telephone communication with the surgical team.
Authors: Adrienne Nicole Hawkins Baksh, Armin Shahrokni
Journal: Journal of Clinical Oncology (2017)

102 Background: In attempts to improve outcomes for and survival of geriatric oncology patients, studies have demonstrated the utility of phone communication as a tool for post-operative care. However, very little data is available to determine if this method of care is reaching the most vulnerable patients. The purpose of this study is to compare patient-surgical team phone communication for geriatric cancer patients of higher and lower preoperative functional status. Methods: This is a retrospective review of data from an internal geriatric assessment questionnaire and phone log data as recorded in the EHR at a single institution. Patients were stratified into two groups: those who had at least one recorded postoperative care phone call (PC) and those with no postoperative care phone call (NPC). Quantitative analysis of the data was performed, assessing the correlation between preoperative functional status and patient-surgical service communication in the first 30 postoperative days. Results: NPC group patients were more likely to be amongst the more frail patients, with lower preoperative functional status and a higher level of distress. Specifically, patients in the NPC group were more likely to be dependent for ADLs (61.0% vs. 50.8%, P = 0.013) and IADLs (59.6% VS. 44.7%, P = 0.001), and have a lower Karnofsky Performance Scale score (46.2% vs. 39.1%, P = 0.048) and also reported a higher level of distress (4.5 vs. 4.00, P = 0.001). There was a trend toward more cognitive impairment among the NPC group compared to the PC group (18.2% vs. 12.1%, P = 0.058). Conclusions: Our study highlights a disparity in the utilization of patient-surgical team phone calls as a method for postoperative care for more frail patients. Despite significant number of phone calls initiated during the postoperative period, mainly by surgical nurses, frail and distressed patients are more likely not to participate in a call. Future studies of postoperative phone communication with geriatric oncology patients should assess the utility of this tool for more frail patients and seek measures that will increase access and participation among this population.
Driving quality improvements of radiation treatment services through a centralized performance management approach.
Authors: Victoria Karuna Hagens, Eric Gutierrez, Yidan Xie, Michelle Ang, Vicky Simanovski, Padraig Richard Warde, Garth Matheson
Journal: Journal of Clinical Oncology (2017)

188 Background: Radiation treatment services are delivered in 16 facilities spread across the province of Ontario, centralized through Cancer Care Ontario’s oversight of quality of care, equipment, hospital funding, clinical and technical guidelines. Methods: In order to ensure high quality care, Cancer Care Ontario employs a systematic approach performance management, whereby facilities are held accountable to achieving provincial quality targets. For radiation treatment, the quality improvement priorities that have leveraged this approach over the last 10 years have included: reduction of wait times to consultation; reduction of wait times to start of treatment; adoption of Intensity Modulated Radiation Therapy (IMRT) where appropriate; and implementation of peer review for treatment plans. In each case, key performance indicators were developed for use in provincial scorecards designed to focus the attention of local clinical and administrative leadership. Regular performance discussions with senior leaders took place throughout implementation, and targeted intervention occurred with facilities that were lagging behind their peers. Results: See table. Conclusions: The ability to centrally monitor the implementation of quality improvement initiatives across a large jurisdiction, and to hold the leadership of each facility accountable to provincial targets through regular feedback and escalation, has been a key component of highly successful change management initiatives in radiation treatment in Ontario. [Table: see text]
Preoperative window-of-opportunity (WOO) study of dacomitinib (Dac) in patients (Pts) with resectable oral cavity squamous cell carcinoma (OCC): Generation of a gene expression signature (DGS) as a predictor of Dac activity.
Authors: Irene Brana, Desmond She, Nicole Grace Chau, Nhu-An Pham, Lucia Kim, Shingo Sakashita, Christine Ng, ChangQi Zhu, Albiruni R. A. Razak, Eric Chen, Lisa Wang, Bayardo Perz-Ordonez, Eric Winquist, Sebastien J. Hotte, Ming-Sound Tsao, Lillian L. Siu
Journal: Journal of Clinical Oncology (2014)

6041 Background: Dac is a potent, irreversible oral pan-HER tyrosine kinase inhibitor (TKI) with activity demonstrated in a multi-center phase II trial as first-line treatment in pts with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) (NCT01449201; Razak et al. Ann Oncol 2013). No predictive biomarkers currently exist for Dac. Methods: WOO is a single-center, investigator-initiated study which enrolled pts with untreated resectable OCC, ECOG 0-2, and adequate organ functions. Pts were randomized 2:1 to Dac 45 mg or placebo QD for 7-11 days prior to surgery. Pre- and post-treatment (surgical specimen) samples were collected. Study objectives: (1) to evaluate a gene expression signature as a predictor of response to Dac, (2) to assess Ki67 modulation by Dac on paired tumor samples. DGS generation and validation: Using pre- and post-treatment fresh tumor biopsies from 7 pts in the NCT01449201 study as a discovery set, DASL HT12 Illumina gene expression array was performed on RNA. Genes differentially expressed in two groups were identified: pre- vs. post-treatment samples and pts with short vs. long progression-free survival (< 10 weeks vs. > 10 weeks). Genes commonly deregulated in both groups defined the signature DGS. DGS was then applied to pre-treatment samples from the WOO study as a validation, blinded to clinical response. Euclidean distance was used for complete-linkage clustering. Results: 14 pts were enrolled in the WOO study with evaluable samples from 10 pts (Dac/Placebo 8:2; response: yes/no/unknown 4/5/1). In the discovery set, a signature of 47 commonly-deregulated genes was found to be capable of dividing patients as high- or low-expressers pre-treatment. Patients clustered as high-expressers were more likely to be good-responders after treatment (RR = 3.75, 95% C.I. 0.8-21.7). No difference was observed in pre- post-treatment Ki67 between pts on Dac or placebo, nor between responders and non-responders. Conclusions: DGS may identity a subgroup of SCCHN pts more likely to respond to Dac; further validation in other Dac-treated SCCHN pts is ongoing. Clinical trial information: NCT01116843.
Review of 200 consecutive patients with mutation profiling in a lung cancer individualized medicine clinic.
Authors: Michael Asiedu, Julian R. Molina, Jin Jen, Jin Sung Jang, Anja Roden, Marie-Christine Aubry, Tobias Peikert, Fabien Maldonado, Charles Thomas, Eric Edell, Wang Lifeng, Ping Yang, Mark S. Allen, Claude Deschamps, Francis C Nichols, Stephen D. Cassivi, Robert Shen, Dennis A. Wigle
Journal: Journal of Clinical Oncology (2013)

e19013 Background: Mutation profiling to assess for potentially druggable mutations in NSCLC is being offered at an increasing number of cancer centers throughout North America and internationally. Although data continue to accumulate for the potential value of mutation testing in designing chemotherapeutic regimens, the treatment impact of obtaining information beyond assessment of EGFR and ALK status remains unclear. How best to obtain and clinically utilize these data, including information from exome and whole genome sequencing, also remains unclear. Methods: Patients were reviewed electronically in a multidisciplinary conference regarding indications for testing and results of mutation profiling from various methods, including the mass-spec based LungCarta test, targeted NexGen sequencing, exome, and whole genome sequencing. Outcomes of the multidisciplinary review were communicated back to treating physicians. Results: Mutation testing was performed on 200 patients using a variety of approaches. The majority (&gt;150) were surgically resected stage I and II tumors. Mutations in at least 1 major cancer driver gene, including EGFR, KRAS, MET, BRAF and PIK3CA, were found in 47% of all patients tested. EGFR mutations were present in 14.8% of patients tested, KRAS 21.3%, BRAF 2.6%, PIK3CA 3.2%, and MET 4.5%. A total of 8 patients underwent either exome or whole genome sequencing. A limited number of patients (&lt;10) had mutation results that impacted treatment decisions from this cohort. Conclusions: Mutation profiling can influence treatment decisions in NSCLC, but at a low frequency. The role of exome and or whole genome sequencing for patients with NSCLC is evolving and remains undefined.
Quality of life outcomes of advanced colorectal cancer in an integrative treatment setting: The Cancer Treatment Centers of America experience
Authors: C. G. Lis, D. Gupta, R. D. Levin, J. Granick, R. Neelam, S. Hoffman, P. G. Vashi, C. A. Lammersfeld
Journal: Journal of Clinical Oncology (2004)

3694 Background: Cancer patients undergoing aggressive chemotherapy can sometimes experience an initial deterioration in quality of life (QoL). In this study we investigated the QoL outcomes of advanced colorectal cancer patients during the first three months of chemotherapy. Methods: We evaluated a case series of 31 stages III-IV colorectal cancer patients treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center between March 2001 and January 2003. All patients underwent a comprehensive program of nutritional, spiritual, physical, naturopathic, and emotional support while receiving aggressive chemotherapy. QoL was evaluated using the EORTC-QLQ-C30 (EORTC) and the Ferrans and Powers Quality of Life Index (QLI). The mean QoL scores were compared using Analysis of Variance across three different time periods; baseline, 1 and 3 months. Results: Patients received a variety of chemotherapy regimens; 12 (38.7%) received leucovorin (lv)-floxuridine (dr)-mitomycin-cisplatin; 6 (19.4%) lv-dr-mitomycin; 5 (16.1%) lv-5 fluorouracil; 4 (12.9%) lv-dr; 3 (9.7%) lv-dr-camptosar and 1 (3.2%) oxaliplatin. Mean QoL scores in both EORTC and QLI showed no significant difference across the three time periods. Conclusions: In this cohort, we found that QoL was well-maintained throughout the first three months of chemotherapy in our integrative cancer treatment setting. These results warrant further investigation to better describe the impact of integrative care on the QoL of these patients. No significant financial relationships to disclose.
A prognostic nomogram for prediction of recurrence following surgical resection of desmoid tumors.
Authors: Aimee Marie Crago, Brian Denton, James J. Mezhir, Meera Hameed, Mithat Gonen, Samuel Singer, Murray F. Brennan
Journal: Journal of Clinical Oncology (2012)

10015 Background: Desmoid tumors can respond to novel chemotherapeutics (e.g., sorafenib). We sought to construct a postoperative nomogram identifying desmoid patients who are at high-risk for local recurrence and potential candidates for systemic therapy. Methods: Desmoid patients undergoing resection from 1982-2011 were identified from a single-institution prospective database. Cox regression analysis was used to create a desmoid-specific recurrence nomogram integrating clinical risk factors. Results: Desmoids were treated surgically in 495 patients (median follow-up 60 months). Of 439 patients undergoing complete gross resection, 100 recurred (92 within 5 years of operation). Five-year recurrence-free survival (RFS) was 71%. Only 8 patients died of disease, all after R2 resection (6 with intraabdominal desmoids). Radiation was associated with worse RFS (p&lt;0.001). Multivariate analysis suggested associations between recurrence and extremity location, young age, and large tumors, but not margin (Table). Abdominal wall tumors had the best outcome (5-year RFS 92% vs. 34% in patients &lt;25y.o. with large, extremity tumors). Age, site and size were used to construct an internally-validated nomogram (concordance index 0.703). Integration of margin, gender, depth, and presentation status (primary vs. recurrent disease) did not improve concordance significantly (0.707). Conclusions: A postoperative nomogram including only size, site and age predicts local recurrence and aids in counseling patients. Systemic therapies may be tested in young patients with large, extremity desmoids, but surgery alone is curative for most abdominal wall lesions. [Table: see text]
Pazopanib in uterine sarcoma (UtS): Review of two European Organisation for Research and Treatment of Cancer (EORTC) and GSK clinical trials 62043 and 62072 on pazopanib for soft tissue sarcoma (STS).
Authors: Isabelle Laure Ray-Coquard, Stefan Sleijfer, Saskia Litière, Jean-Yves Blay, Axel Le Cesne, Zsuzsanna Papai, Ian Robert Judson, Patrick Schoffski, Sant P. Chawla, Thierry Gil, Sophie Piperno-Neumann, Sandrine Marreaud, Rachel Hodge, Winette T.A. Van Der Graaf
Journal: Journal of Clinical Oncology (2014)

10579 Background: Pazopanib has been introduced recently in the treatment for patients with advanced STS. Multiple chemotherapies have been investigated for the treatment of advanced and recurrent UtS, but most of them result in only moderate response rates (RR) and duration. Methods: In this retrospective analysis we investigated the outcome of UtS pts treated with pazopanib in the two EORTC clinical trials, the phase II 62043 (n= 142) and the phase III trial 62072
And How Long Will You Be Staying, Doctor?
Authors: Heather Kovich
Journal: New England Journal of Medicine (2017)

Interview with Dr. Heather Kovich on the challenges facing patients and physicians in rural areas of the United States. (10:07)Download A rural physician hears that question from her patients at every visit. It implies what the Dartmouth Atlas makes explicit: physician supply is driven by where physicians want to live, not by the health needs of the community. If the doctors like it, maybe they'll stay.
Serologic and immunologic studies in patients with AIDS in North America and Africa. The potential role of infectious agents as cofactors in human immunodeficiency virus infection
Authors: T. C. Quinn
Journal: JAMA (1987)

Serologic and immunologic studies were performed in 38 African and 60 US patients with acquired immunodeficiency syndrome (AIDS), 100 African and 100 US heterosexual men and women, and 100 US homosexual men to examine the potential role of infectious agents in human immunodeficiency virus (HIV) infection. There were no significant differences in the prevalence of antibodies to cytomegalovirus, Epstein-Barr virus, hepatitis A and B viruses, herpes simplex virus, syphilis, and toxoplasmosis among the African and US patients with AIDS, African heterosexual controls, and US homosexual men. However, these four groups all demonstrated a significantly greater prevalence of antibodies to each of these infectious agents compared with US heterosexual men. Immunologic studies demonstrated a significant elevation of activated lymphocytes (HLA-DR and T3 positive) and immune complexes in both AIDS populations and African heterosexual and US homosexual populations, compared with the US heterosexual population. These data demonstrate that the immune systems of African heterosexuals, similar to those of US homosexual men, are in a chronically activated state associated with chronic viral and parasitic antigenic exposure, which may cause them to be particularly susceptible to HIV infection or disease progression. (<i>JAMA</i>1987;257:2617-2621)
Randomized phase III trial of neoadjuvant chemotherapy (CT) in head and neck (H&amp;N) cancer patients: An update based on 10 years' follow up
Authors: P. L. Zorat, L. Loreggian, A. Paccagnella, A. Gava, C. A. Mione, F. Bordin, C. Marchiori, G. L. Pappagallo, L. Tomio
Journal: Journal of Clinical Oncology (2004)

5532 Background: In 1986, the Gruppo di Studio sui Tumori Testa e Collo (GSTTC) started a multicenter randomized trial comparing induction CT with Cisplatin and 5Fluorouracil 120h c.i. (PF) followed by locoregional treatment (Surgery+RT or RT alone) (Group A) versus locoregional therapy (LRT) alone (Group B) in resectable or unresectable stage III-IVM0 H&N Squamous Cell Carcinoma. Our previous report (J Natl Cancer Inst 86: 265–72,1994), showed that 4 cycles of PF before LRT improved local control, decreased the incidence of distant metastases and increased Disease-Free-Survival (DFS) and Overall Survival (OS) in the subgroup of inoperable patients. Methods: From March 1986 to February 1990, 237 patients with stage III-IVM0 were randomized to 4 neoadjuvant PF followed by LRT or LRT alone. After a minimum follow-up of 10 years, the two treatments were compared in univariate and multivariate analysis for OS. Results: Of the 237 patients, 118 group A and 119 group B, 92% and 90% respectively were male, 25% and 28% hypopharynx, 59% and 54% oropharynx, 15% and 16% oral cavity. KPS ≥70 in 95% and 92%; stage III 35% and 37%. Inoperable 71% and 73%. The OS for the entire group of patients at 5 and 10 years was 23% and 19% for Group A and 16% and 9% for Group B (p=0.13). No difference was observed in operable patients. In inoperable patients, the OS at 5 and 10 years was 21% and 16% for Group A and 8% and 6% for RT arm (p=0.04). With Cox analysis applied to all randomized patients, the HR and p values were respectively 1.251 and 0.292 for site; 3.28 and 0.002 for T; 1.66 and 0.036 for N; 0.92 and 0.56 for treatment arm. Conclusion: The analyses at 10 years has confirmed all the previously reported data. Four cycles of neoadjuvant CT remains a promising approach for advanced H&N cancer with a significant OS advantage in inoperable patients. No significant financial relationships to disclose.
Preparing for bundled payments in urology: Defining episodes, evaluating variations in care, and demonstrating improved value.
Authors: Eila C. Skinner, Ning Tang, Kerri Stevenson, David Guo, Jui-Shan Hu, Joan Hendershott, Purnima Krishna
Journal: Journal of Clinical Oncology (2017)

11 Background: As payors introduce APMs, there is little guidance on how episodes will be defined in subspecialty areas. We set out to define clinically relevant episodes of care, develop standardized approachs toward reducing variations in care, and implement evidence-based standardized care pathways. We chose two urologic cancer procedures- Radical Cystectomy and Robotic Radical Prostatectomy. Methods: Episode timeframes were defined: Radical Cystectomy (14 days prior, index hospitalization, 90 days post) and RALP (30 days prior, index hospitalization, 30 days post). To identify variations in care, we compared evidence-based guidelines with practice patterns, analyzed episode and index hospitalization direct costs for various surgeons, and reviewed the utilization of high cost supplies and drugs. Length of stay (LOS), readmissions, complications, and acuity were benchmarked against comparable academic medical centers. Faculty, trainees, APPs, and staff collaborated to develop care pathways, modify workflows and EPIC order sets to reduce variation, improve outcomes, and increase efficiency. Results: Variation in care was reflected in wide standard deviations in episode direct costs. Six months after implementing care pathways, we achieved the following: RALP average cost per episode decreased by 15%. Standard deviation in episode direct costs decreased by 77%. The percentage of patients with 1-day LOS increased from 21% to 67%. The medical surgical supply costs during hospitalization decreased by 22.5%. Standard deviation in episode direct costs for Radical Cystectomy decreased by 27%. Readmissions to SHC decreased from 15.6% to 12.5%. The percentage of patients with less than 6-day LOS increased from 46% to 66%. Conclusions: Across two episodes, our care redesign efforts had actualized direct cost savings of $692,000 annually. As we prepare for future APMs, similar multidisciplinary approaches can be applied to other areas to reduce costs and improve quality of care.