tbuckley/cabot-search huggingface dataset:
Underuse of cancer-directed care in Medicaid patients with esophageal cancer.
Authors: Sha'Shonda L. Revels, Rishinda Reddy, Sandra L. Wong
Journal: Journal of Clinical Oncology (2013)

6637 Background: Among esophageal cancer (EC) patients (pts) there are significant disparities in the use of cancer directed-treatments. We examined the extent to which insurance status explains treatment choices and survival differences. Methods: Using the National Cancer Database Participant User File, we identified 94,399 EC pts (36% private insurance [PI], 51% Medicare, 6% Medicaid and 3% uninsured [UI]), treated at 1,586 hospitals, diagnosed 1998-2010. We evaluated variations in the use of chemotherapy, radiation and surgery with logistic regression. Cox proportional hazards regression was used to assess differences in survival. Models were adjusted for pt and tumor characteristics, as well as clustering. Results: Compared to PI pts, Medicaid pts were more likely to live in neighborhoods with low educational attainment (36 vs. 14%, p&lt;0.01), have annual incomes &lt;$30,000 (32 vs. 11% p&lt;0.01) and present with stage III EC (37 vs. 17%, &lt;0.01). Despite adjustment for pt, tumor and hospital characteristics, Medicaid pts with non-metastatic EC were less likely to undergo surgery (OR 0.43, 95% CI 0.37-0.50) and chemotherapy (OR 0.71, 95% CI 0.60-0.84) compared to PI pts. There were no differences in the use of radiation. Hospital resection rates were inversely related to Medicaid/UI case mix. The risk-adjusted resection rate for Medicaid pts at hospitals with relatively few Medicaid/UI pts was 42%, compared to 33% in hospitals with higher case mix (p&lt;0.01). Pts at hospitals with higher Medicaid/UI case mix experienced poorer risk-adjusted survival (HR 1.16, 95% CI 1.11-1.23). Survival differences were attenuated after accounting for receipt of surgery (HR 1.09, 95%CI 1.04-1.15), but not for chemotherapy or radiation. Conclusions: Poorer survival among pts treated at hospitals with high Medicaid/UI case mix is, in part, related to the underuse of surgery. Reducing cancer deaths in disadvantaged populations will require stakeholders to gain an understanding of why these pts are less likely to get to the operating room. In addition, steps must be taken to assure that hospitals with higher Medicaid/UI case mixes are equipped to provide quality cancer care, particularly in light of upcoming Medicaid expansion.
Patterns of care for 1,602 patients with newly diagnosed glioblastoma.
Authors: Luc Bauchet, Sonia Zouaoui, Amelie Darlix, Valerie Rigau, Helene Mathieu-Daude, Pascale Fabbro-Peray, Michel Fabbro, Johan Pallud, Faiza Bessaoud, Fabienne Bauchet, Marie Charissoux, Aymeric Amelot, Emmanuel Mandonnet, Olivier L. Chinot, Dominique Figarella-Branger, Francois Labrousse, Brigitte Tretarre, Luc Taillandier
Journal: Journal of Clinical Oncology (2015)

e13005 Background: This work describes oncological patterns of care and survival for all patients (pts) with newly diagnosed histologically confirmed glioblastoma (GB) in metropolitan France in 2008. Methods: The French Brain Tumor DataBase identified all newly diagnosed and histologically confirmed GB pts in 2008, and prospectively collected initial data. Data on care management and follow-up were retrospectively collected on a dedicated file from 2008/01/01 to 2013/01/01. Results: 2057 GB pts [males/females 1.5, median age 63 yrs, median preoperative Karnofsky performance status (KPS) 80] were included from all academic and private healthcare institutions in metropolitan France (population: 62 134 866 inhabitants, crude rate: 3.31 per 100,000). Complete treatment information was available for 1602 pts. Surgery consisted of resection (RS): 962 pts (including 123 pts with BCNU wafer implantation) and biopsy (B): 640 pts. 282 pts had no subsequent oncological treatment. After surgery, first line treatment (n = 1320) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant (RT-TMZ) in 947 pts [plus adjuvant TMZ (RT-TMZ+aTMZ) in 770 pts, with < 6 cycles in 407 pts, 6 cycles in 200 pts, > 6 cycles in 163 pts], RT alone in 93 pts, and chemotherapy alone in 280 pts. The median survival (MS) of the cohort was 334 days [95%CI, 317-354] significantly impacted by age, KPS and tumor location. In the group of RT-TMZ+aTMZ, MS (days, [95%CI]), when analyzed by specific subgroups, were as followed: - B (n = 181): 453 [385-538], RS (n = 589): 583 [560-626], p = 0.0004, - Total and subtotal RS with BCNU wafer (n = 50): 795 [528-1062], without BCNU wafer (n = 314): 580 [536-624], p = 0.08, - 6 cycles of aTMZ (n = 200): 708 [645-771], > 6 cycles of aTMZ (n = 163): 833 [688-978], p < 0.001, - At progression, 377 pts were treated with bevacizumab (BEV) alone or in association, and 393 pts were treated without BEV, MS were 627 [596-658] and 443 [385-501] respectively, p = 0.057; and among pts who had a primary RS, 99 pts were treated with second RS and 490 were treated without, MS were 811 [665-957] and 558 [527-588], p < 0.001. Conclusions: Population study at national level is very useful to evaluate daily clinical practices in the framework of care management for pts with GB.
Risk of peritoneal carcinomatosis in localized gastric adenocarcinoma patients who undergo preoperative therapy and attempted surgery.
Authors: Dilsa Mizrak Kaya, Graciela M. Nogueras-Gonzalez, Kazuto Harada, Mariela A. Blum Murphy, Prajnan Das, Bruce D. Minsky, Jeannelyn Estrella, Quan Lin, Fatemeh Ghazanfari Amlashi, Jeffrey H Lee, Brian Weston, Manoop S. Bhutani, Carol C Wu, Aurelio Matamoros, Tara L. Sagebiel, Paul F. Mansfield, Brian D. Badgwell, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2017)

104 Background: Positive peritoneal cytology (+PCyt) or gross peritoneal carcinomatosis (GPC) carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended for all ≥T1b GACs. The natural history of GAC patients who have baseline –PCyt and then undergo multimodality therapy is not well documented, particularly for the risk of subsequent GPC. Methods: We analyzed 178 GAC patients with -PCyt at baseline who were followed postoperatively. Results: Of 178 patients who went to surgery after preoperative therapy, surgery in 14 patients (7.9%) was aborted due to GPC in 13 patients, and liver metastases in 1. We then analyzed 164 patients who had an R0 resection. The median follow-up duration was 3.4 (0.6-18) years. The rate of subsequent GPC was 13.4%, (22/164 patients) and the median time to GPC was 15.6 months. The median overall survival (OS) after GPC was only 7.1 months (95% CI: 0.4-17.9 months). Various clinical variables were related with GPC after an R0 resection (Table 1). The 5-year OS rate for patients without subsequent GPC was 75%. Conclusions: Even with baseline –PCyt, subsequent risk for GPC is ~20% in the best group of localized GAC patients. Patients who do not develop GPC have an excellent (75%) OS rate. Further research is warranted to identify patients at high risk of subsequent GPC. [Table: see text]
CPX-351 for the Treatment of High-Risk Patients with Acute Myeloid Leukemia
Authors: Rita Assi, Hagop M. Kantarjian, Srdan Verstovsek, Guillermo Garcia-Manero, Marina Konopleva, Farhad Ravandi, Courtney D DiNardo, Tapan M. Kadia, Naval Daver, Elias J. Jabbour, Rosilyn A. Gborogen, Kamal Chamoun, William G. Wierda, Gautam Borthakur, Jorge E. Cortes
Journal: Blood (2016)
Association between cancer-related fatigue and other symptoms in breast cancer patients.
Authors: Anita Roselyn Peoples, Charles E. Heckler, Joseph A. Roscoe, Charles Stewart Kamen, Luke Joseph Peppone, Karen Michelle Mustian, Michelle Christine Janelsins, Dennis Frederic Moore, Charlotte Coles, Karen L. Hoelzer, Jacqueline P Williams, Gary R. Morrow
Journal: Journal of Clinical Oncology (2013)

e20526 Background: Cancer-related fatigue (CRF) is one of the most prevalent side effects of cancer treatment and has a detrimental effect on a patient’s normal functioning and quality of life. At present, the underlying pathophysiology of CRF is poorly understood, as it is complex phenomenon involving the interaction of many factors. The relative contributions of the disease itself, different cancer therapies, and comorbid conditions (e.g., sleep disorders, nausea) remain unclear. Therefore, it is important to understand the association between them in order to develop better strategies for the prevention and treatment of CRF. Methods: The purpose of these secondary analyses was to examine the association between post-treatment fatigue with disturbed sleep (on a 0–10 scale), delayed nausea (on a 1–7 scale), age, and baseline fatigue. Analyses were performed on 541 breast cancer patients (mean age 54, 100% female) who completed a four-day diary assessing nausea and sleep following initial chemotherapy. Fatigue as its worst during the prior week (0 = no fatigue to 10 = fatigue as bad as you can imagine) was assessed both prior to chemotherapy and on Day 4. To determine associations between variables, Pearson’s correlation analysis and linear regression were performed. Results: Post-treatment CRF was significantly associated with baseline fatigue (r = 0.40, p &lt; 0.0001), disturbed sleep (r = 0.45, p &lt; 0.0001), delayed nausea (r = 0.37, p &lt; 0.0001), and age (r = -0.22, p &lt; 0.0001). Linear regression showed that a one unit increase in baseline fatigue, disturbed sleep, and delayed nausea was associated with increase in post-treatment CRF by 0.29, 0.37, and 0.42, respectively, all p’s &lt; 0.0001. In addition, every ten years of increased age was associated with a decrease in post-treatment CRF by 0.33 (p &lt; 0.0013). Conclusions: Post-treatment fatigue was found to be significantly correlated with baseline fatigue, disturbed sleep, and delayed nausea while negatively correlated with age in patients with breast cancer. These results demonstrate the importance of further research to better understand the underlying psychological and biological mechanisms for CRF in order to develop effective treatments. Supported by NCI grant CA37420.
Outcomes for patients ≥75 years with localized gastroesophageal cancer: Experience from the Princess Margaret Cancer Centre.
Authors: Akina Natori, Bryan Anthony Chan, Hao-Wen Sim, Lucy Xiaolu Ma, Daniel Yokom, Eric Xueyu Chen, Geoffrey Liu, Gail Elizabeth Darling, Carol Jane Swallow, Savtaj Singh Brar, James D. Brierley, Jolie Ringash, Rebecca Wong, John Kim, Patrik Rogalla, Sara Hafezi-Bakhtiari, James Conner, Jennifer J. Knox, Elena Elimova, Raymond Woo-Jun Jang
Journal: Journal of Clinical Oncology (2017)

10037 Background: The optimal treatment and outcome for elderly patients (pts) with localized gastroesophageal (GE) cancer remains unclear as they are underrepresented in clinical trials. We aimed to assess survival in pts ≥75 years according to treatment received. Methods: A retrospective analysis was performed for all pts aged ≥75 years with GE cancer treated in 2012-2014. Frailty was measured using the Charlson comorbidity index (CCI) and ECOG performance status (PS). Overall survival (OS) and disease-free survival (DFS) were assessed via uni- and multivariable Cox proportional hazards regression, adjusting for demographics. Logistic regression analyses were used to examine factors impacting treatment choices. Results: Of 105 pts, median age was 81 years (range: 75-99), primary sites were esophageal (55%, with 43% squamous histology) and gastric (45%). Baseline characteristics included: PS: 0 (31%), 1 (42%), 2 (16%), 3 (10%), 4 (1%); and CCI: 0 (34%), 1 (25%), 2 (19%), ≥3 (22%). Treatment received included radiotherapy alone (RT) (31%); surgery alone (29%); surgery plus adjuvant chemotherapy (chemo) and/or RT (14%); chemoradiation alone (7%) and supportive care (18%). In univariable analyses; age &lt; 85 (p = 0.003), PS &lt; 2 (p = 0.03) and surgery (p &lt; 0.001) were associated with improved OS. Chemo and RT, either alone or in combination, did not significantly improve OS. In multivariable analyses; surgery (HR 0.38, 95% CI 0.21-0.70, p = 0.002) was the only independent predictor for improved OS. Patients with good PS (p = 0.01), gastric disease site (p = 0.01) and adenocarcinoma histology (p = 0.02) were more likely to undergo surgery. Conclusions: At our institution, relatively few pts ≥75 years received multimodality therapy for localized GE cancers. Those pts ≥75 years who underwent surgery had excellent outcomes, but they were well-selected. Comprehensive assessment should be considered for pts ≥75 years with localized GE cancer to ensure optimal treatment selection, particularly given the potential benefit of surgery.
Evaluation of the prognostic/predictive role of tumor EGFR and KRAS mutations in Greek metastatic non-small cell lung cancer patients treated with first-line chemotherapy.
Authors: Helena Linardou, Paris A. Kosmidis, Vassiliki Kotoula, Vasilios Karavasilis, Anastasia G Eleftheraki, Georgios Lazaridis, Emily Daskalaki, Sotiris Lakis, Elpida Charalambous, Epaminontas Samantas, Dimitrios G. Pectasides, Dimitris Bafaloukos, George Fountzilas
Journal: Journal of Clinical Oncology (2013)

e19048 Background: KRAS mutations are reported in 20-25% of non-small cell lung cancer (NSCLC). Little is known about the prognostic/predictive role of KRAS in advanced NSCLC, with conflicting results among small studies. Recent evidence showed that KRAS mutations could predict for worse outcome in patients treated with platinum-based adjuvant chemotherapy. Methods: KRAS and EGFR genotypes were evaluated in 414 NSCLC patients with available clinical data, diagnosed from March 2000 to December 2012 (tissue blocks from the HeCOG tumor repository). KRAS and EGFR mutations were associated with clinicopathological parameters (mutated vs. wild-type). Outcome comparisons were performed in 214 metastatic patients with treatment data available, following 1 st -line chemotherapy without tyrosine kinase inhibitors. Results: The majority of the patients were male (80%), current smokers (53%), with adenocarcinoma (AC) histology (65%). EGFR mutations were found in 10% and KRAS mutations in 17% of all histological types, while in AC they were 14% and 21%, respectively. Most EGFR mutations were classical (79%), while most common KRAS mutations were p.G12C (39%), p.G12D (30%) and p.G12V (15%). Two tumors had concurrent EGFR and KRAS mutations. EGFR mutations were significantly associated with female gender, AC histology and non-smoking status, as previously described. KRAS mutations were associated with AC histology and younger age (&lt;60). At a median follow-up of 31 months, EGFR status did not show any significant associations with OS or PFS, while KRAS mutations were prognostic for worse OS compared to KRAS and EGFR wild-type tumors (HR=1.67, CI=1.08-2.59, p=0.021). This effect was also significant (p=0.022) in the presence of treatment type, with platinum-based therapy being a positive prognostic factor for OS (HR=0.62, CI=0.4-0.92, p=0.019). The association of KRAS mutations with PFS was not significant. Conclusions: EGFR and KRAS genotype incidences are presented for the first time for Greek metastatic NSCLC patients. In this setting, the presence of KRAS mutations significantly increases and platinum 1 st -line treatment decreases the risk of death.
Functional Neuroimaging Predictors of Self-Reported Psychotic Symptoms in Adolescents
Authors: Josiane Bourque, Philip A. Spechler, Stéphane Potvin, Robert Whelan, Tobias Banaschewski, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Vincent Frouin, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère-Martinot, Sarah C. McEwen, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Michael N. Smolka, Nora C. Vetter, Henrik Walter, Gunter Schumann, Hugh Garavan, Patricia J. Conrod
Journal: American Journal of Psychiatry (2017)

Objective: This study investigated the neural correlates of psychotic-like experiences in youths during tasks involving inhibitory control, reward anticipation, and emotion processing. A secondary aim was to test whether these neurofunctional correlates of risk were predictive of psychotic symptoms 2 years later. Method: Functional imaging responses to three paradigms—the stop-signal, monetary incentive delay, and faces tasks—were collected in youths at age 14, as part of the IMAGEN study. At baseline, youths from London and Dublin sites were assessed on psychotic-like experiences, and those reporting significant experiences were compared with matched control subjects. Significant brain activity differences between the groups were used to predict, with cross-validation, the presence of psychotic symptoms in the context of mood fluctuation at age 16, assessed in the full sample. These prediction analyses were conducted with the London-Dublin subsample (N=246) and the full sample (N=1,196). Results: Relative to control subjects, youths reporting psychotic-like experiences showed increased hippocampus/amygdala activity during processing of neutral faces and reduced dorsolateral prefrontal activity during failed inhibition. The most prominent regional difference for classifying 16-year-olds with mood fluctuation and psychotic symptoms relative to the control groups (those with mood fluctuations but no psychotic symptoms and those with no mood symptoms) was hyperactivation of the hippocampus/amygdala, when controlling for baseline psychotic-like experiences and cannabis use. Conclusions: The results stress the importance of the limbic network's increased response to neutral facial stimuli as a marker of the extended psychosis phenotype. These findings might help to guide early intervention strategies for at-risk youths.
Differential Induction of Immunogenic Cell Death and Interferon Expression in Cancer Cells by Structured ssRNAs
Authors: Jaewoo Lee, Youngju Lee, Li Xu, Rebekah White, Bruce A. Sullenger
Journal: Molecular Therapy (2017)

Activation of the RNA-sensing pattern recognition receptor (PRR) in cancer cells leads to cell death and cytokine expression. This cancer cell death releases tumor antigens and damage-associated molecular patterns (DAMPs) that induce anti-tumor immunity. However, these cytokines and DAMPs also cause adverse inflammatory and thrombotic complications that can limit the overall therapeutic benefits of PRR-targeting anti-cancer therapies. To overcome this problem, we generated and evaluated two novel and distinct ssRNA molecules (immunogenic cell-killing RNA [ICR]2 and ICR4). ICR2 and ICR4 differentially stimulated cell death and PRR signaling pathways and induced different patterns of cytokine expression in cancer and innate immune cells. Interestingly, DAMPs released from ICR2- and ICR4-treated cancer cells had distinct patterns of stimulation of innate immune receptors and coagulation. Finally, ICR2 and ICR4 inhibited in vivo tumor growth as effectively as poly(I:C). ICR2 and ICR4 are potential therapeutic agents that differentially induce cell death, immune stimulation, and coagulation when introduced into tumors.
VEGF Specific siRNAs Act Synergistically with Bortezomib and Steroids in Inhibiting VEGF Gene Expression, Proliferation and Induction of Apoptosis in Multiple Myeloma Cells.
Authors: Michael Koldehoff, Nina K. Steckel, Rudolf Trenschel, Dietrich W. Beelen, Ahmet H. Elmaagacli
Journal: Blood (2004)
Prognostic significance of second mitochondria-derived activator of caspase expression in bladder cancer and target for therapy.
Authors: Yoichi Mizutani, Haruhito Azuma
Journal: Journal of Clinical Oncology (2012)

e15000 Background: Although the expression of second mitochondria-derived activator of caspase (Smac/DIABLO) has been reported in various cancers, little is known about its clinical significance in bladder cancer. The present study was designed to evaluate the relationship between progression of disease and Smac/DIABLO expression by clinical pathological analysis of patients with bladder cancer. Methods: The level of Smac/DIABLO expression was quantified by western blot analysis using non-fixed fresh frozen tissues derived from patients with bladder cancer. Results: All normal bladders expressed Smac/DIABLO. However, 64/84 ( 76% ) of bladder cancers expressed Smac/DIABLO and 24% were negative. In Ta and T1 superficial bladder cancers, 98% expressed Smac/DIABLO, whereas only 41% expressed Smac/DIABLO in muscle-invasive bladder cancers. Smac/DIABLO expression inversely correlated with the grade of bladder cancer. Patients with Ta and T1 superficial bladder cancer with higher Smac/DIABLO expression had a longer postoperative recurrence-free period than those with lower Smac/DIABLO expression after transurethral resection in the 5-year follow-up. Patients with invasive bladder cancer expressing Smac/DIABLO had a longer postoperative disease-specific survival than those without Smac/DIABLO expression after radical cystectomy in the 5-year follow-up. The cisplatin-resistant T24 bladder cancer line ( T24/CDDP ) and the adriamycin-resistant T24 line ( T24/ADR ) showed lower level of Smac/DIABLO expression, compared with the T24 parental line. Conclusions: The present study demonstrates for the first time that Smac/DIABLO expression was downregulated in bladder cancer, especially in high grade muscle-invasive bladder cancer, and that lower Smac/DIABLO expression in bladder cancer predicted a worse prognosis. In addition, the cisplatin-resistant T24/CDDP line and the adriamycin-resistant T24/ADR line expressed lower level of Smac/DIABLO expression. These results suggest that Smac/DIABLO expression in bladder cancer may be used as a prognostic parameter, and that low Smac/DIABLO expression in bladder cancer may be associated with resistance to chemotherapy.
Surgery for patients receiving ipilimumab: Safety profile and immunological insights.
Authors: David E. Gyorki, Jianda Yuan, Zhenyu Mu, Bushra Zaidi, Humilidad F. Gallardo, Mary Susan Brady, Philip H. Gutin, Daniel G. Coit, Jedd D. Wolchok, Charlotte Eielson Ariyan
Journal: Journal of Clinical Oncology (2012)

8583 Background: Ipilimumab (ipi), a monoclonal antibody blocking CTLA-4, demonstrated survival benefit in metastatic melanoma in two randomized controlled trials. With its approval by the FDA, the use of this immunotherapy is increasing. The surgical safety of ipi has not been reported. Methods: From our prospective database, we identified patients undergoing surgery within 30 days of receiving a dose of ipi or on maintenance ipi between October 2007 and August 2011. Surgical toxicity was graded 1-5 by the Clavien classification. In 10 patients matched blood and tumor infiltrating lymphocytes were harvested. Phenotype of T cell subsets were analyzed by flow cytometry. Results: 23 patients were identified who underwent 34 operations a median of 27 weeks after initiation of ipi (1-123 weeks). Indications for surgery were symptomatic, progressive, or isolated persistent disease in 52%, 39% and 9% respectively. Subcutaneous resections were the most frequent, followed by intra-abdominal and nodal procedures (Table). Grade 1 wound complications were seen in 17% of patients. One patient had a Grade 2 wound complication. No Grade 3-5 complications were seen. With a median follow up from starting ipi of 86 weeks, 3 patients have no evidence of disease, 10 are alive with disease and 10 have died of disease. Analysis of the T cell infiltrate and peripheral blood from 10 patients with progressive or symptomatic disease shows an elevated % of CD4 + FOXP3 + T regulatory cells and a 2.8 fold reduction in CD8 + / CD4 + FOXP3 + T regulatory ratio in the tumor compared to blood (p=0.02). Conclusions: Results from this single-center experience suggest that surgery is safe in patients receiving ipi. Immune modulation caused by CTLA-4 blockade does not appear to impact wound healing, even in the bowel. In carefully selected patients metastectomy may be appropriate for breakthrough metastases. The high percentage of T regulatory cells and low T effector cells in the progressive tumors suggests a mechanism of immune escape. [Table: see text]