tbuckley/cabot-search huggingface dataset:
Retrospective analysis of head and neck cancer patients successfully treated with chemoradiation plus nimotuzumab.
Authors: S. M. Karandikar, K. Bokil, S. P. Deshmukh, S. Basu, B. Shinde, H. Patil, N. Gupta
Journal: Journal of Clinical Oncology (2011)

e16013 Background: Nimotuzumab with chemoradiation is found to be efficacious and safe in treatment of locally advanced squamous cell carcinoma of head and neck (LASCCHN). We did retrospective analysis of head and neck cancer patients at single center treated with this combination from December 2006 to December 2010. Methods: Sixteen patients of SCCHN from stage I to IVa who either were not willing or ineligible for surgical resection, analyzed. Treatment included Cisplatin in dose of (40 mg/m2) once weekly for six weeks; Radiotherapy was used in dose of 60-66 Gy either by conventional radiotherapy or IMRT. Nimotuzumab was used as 200mg Intravenous infusion for 60 minutes, once in a week for 6 weeks. Results:There were 9 male and 7 female patients, (median age, 54 years; range, 29 to 74 years; with ECOG status of 0-1; oropharynx - 11, larynx – 4, hypopharynx – 1, with 2, 5, 3, 6 patients in stages I to IV respectively). All patients completed 6 cycles of treatment with nimotuzumab. The disease control rate at 24 weeks post treatment was 81% with 12 patients in CR, 1 patient in SD, while 3 patients showed progressive disease during second, third, and fifth month of follow up. The overall survival for all patients ranged from 10 months to 33 months till December 2010. There was no grade III or IV adverse event related to nimotuzumab and it was well tolerated. Conclusions: This retrospective analysis supports that nimotuzumab with chemoradiation is an effective and safe treatment for head and neck cancer patients that can lead to long term survival benefits. Large clinical trials are underway to further validate these findings.
Pathways, partners and payers: The trifecta of palliative care integration.
Authors: Diane G. Portman, Sarah Thirlwell
Journal: Journal of Clinical Oncology (2015)

129 Background: Moffitt Cancer Center has developed proprietary oncology clinical pathways. Multiple external partnership agreements which require adoption of these pathways have been completed. Our Center has enacted new cancer care delivery and payment arrangements with payers to foster cost and quality balance via use of the pathways and earlier involvement of palliative care (PC). Methods: Executive and PC leadership collaborated with the clinical pathways and strategic alliance teams to identify high priority disease states for integration of PC. Working with oncologist pathway developers, critical junctures in the pathways for inclusion of PC consultation were proposed and refined. EHR mechanisms to promote pathway adherence by clinicians were initiated. The value of pathway utilization and care coordination to involve PC was promoted to prospective oncology partners and payers. Results: PC has been mandated in oncology clinical care pathways, with a focus on thoracic, breast, gastrointestinal, prostate, gynecologic and hematologic malignancies, as directed by specific payer arrangements. Partnerships have expanded, resulting in greater utilization of PC by other centers as well. Increased referral volumes to PC, broader symptom control, and enhanced advance care planning have resulted. Conclusions: Incorporation of PC in oncologic clinical care pathways, with dissemination to internal providers, external partners and as part of novel payment models, optimizes PC integration. [Table: see text]
Variant isoforms of CD44 expression as predictive markers for mortality in surgically treated patients with locally advanced upper tract urothelial carcinoma.
Authors: Eiji Kikuchi, Masayuki Hagiwara, Nozomi Hayakawa, Ryuichi Mizuno, Takeo Kosaka, Shuji Mikami, Akira Miyajima, Hideyuki Saya, Mototsugu Oya
Journal: Journal of Clinical Oncology (2016)

388 Background: The variant isoforms of CD44 (CD44v), which are some of the new cell surface markers for cancer stem cells, have been associated with tumor growth, treatment resistance, and cancer death in several cancers. We investigated the role of CD44v8-10, which is a CD44v, on the clinical outcome of patients with advanced upper tract urothelial cancer (UTUC). Methods: The protein expression of CD44v8-10 was immunohistochemically evaluated using CD44v9 antibody, which detects immunogen of CD44v8-10, and investigated the association with clinical characteristics and outcome in surgical specimens obtained from 110 patients who had been treated with radical nephroureterectomy for ≥pT2 UTUC. The mean percentage of positive cancer cells stained with CD44v9 antibody in each tumor was estimated. Results: The median percentage of CD44v9 positivity was 5.50±7.74%. Patients were subsequently stratified into a CD44v9-positive group (n = 82) and a CD44v9-negative group (n = 28) based on a cut-off level of 5%. During the mean follow-up of 4.8 years, disease recurrence was observed in 49 patients (59.8%) in the CD44v9-positive group and in 8 patients (28.6%) in the CD44v9-negative group. The 5-year recurrence-free survival rates were 47.6% in the CD44v9-positive group and 66.6% in the CD44v9-negative group (p= 0.038). Multivariate analysis showed that tumor grade G3 (p= 0.005, HR = 3.77), the presence of lymphovascular invasion (p= 0.041, HR = 1.84), and CD44v8-10 expression (p= 0.028, HR = 2.33) were independent risk factors for disease recurrence. In this series, 37 patients in the CD44v9-positive group (45.1%) and 5 (17.9%) in the CD44v9-negative group died of the disease. The 5-year cancer-specific survival rates were 57.8% in the CD44v9-positive group and 80.4% in the CD44v9-negative group (p= 0.032). The CD44v9 expression (p= 0.040, HR = 2.67) in addition to tumor grade G3 (p= 0.003, HR = 8.35) were independently associated with cancer death. Conclusions: The expression ofCD44v8-10 may be a new biomarker of malignant potential in locally advanced UTUC and could provide additional prognostic information in patients with UTUC.
Practice patterns of bevacizumab-induced hypertension in cancer patients.
Authors: Carmelita P. Escalante, Amit Lahoti, Shana L. Palla, Maggie Lu, Michael J. Overman, Marina George, Rana Abisaid Baker, Saketh Palasamudram Shakar, Jean-Bernard Durand
Journal: Journal of Clinical Oncology (2013)

e20664 Background: Vascular endothelial growth factor (VEGF) inhibitors such as bevacizumab (BV) can result in side-effects such as hypertension (HTN), proteinuria and acute kidney injury (AKI). The objectives are to evaluate practice patterns of BV-induced HTN; to assess frequency of BV dose reduction, withdrawal and delay due to HTN, proteinuria and AKI; and to determine the time course for initial resolution of BV-induced HTN, proteinuria and AKI. Methods: We retrospectively reviewed random charts of 75 cancer patients (pts) treated with BV from 1/1/2009 to 9/30/2011. This included demographic, clinical and outcome parameters. Descriptive statistics were utilized. Results: 37 (56%) were males with median age 56 years (range 19-84). Most had lung (14, 19%), breast (11, 15%), and colorectal cancer (10, 13%). 69 (92%)had metastatic disease. 70 (93%) pts were on BV with other antineoplastic agents. 37 (49%) had a diagnosis of HTN at study entry. The median days from first BV treatment (tx) to first hypertensive reading was 7 (0-279) and days to receiving new or dose increase of HTN meds was 49 (0-283). 44 (59%) pts had 2 consecutive readings ≥ 140 or ≥ 90 mmHg during BV tx and 49 (65%) during post-tx follow-up of 6 months or less. 14 pts received new or dose increase of HTN meds during tx. The most frequent HTN meds used were diuretics (26%), beta blockers (21%) and calcium channel blockers (17%). The average number of new HTN meds at last BV tx was 1.5. No pt had BV dose reduced due to HTN, proteinuria or AKI. BV was withdrawn in 2 (3%) due to HTN, 2 (3%) due to proteinuria and 1 (1%) due to AKI. 5 pts had a delay due to HTN (4) and AKI (1). 57% (8 /14) of pts receiving additional HTN meds during BV tx had first dose decrease of additional HTN meds post-tx at a median of 30.5 (11-162) days. The median number of days to resolve first proteinuria and first AKI was 20 (1-193) and 14 (0-34) days, respectively. Conclusions: HTN occurred in a majority with few receiving extra HTN meds although meeting HTN criteria. Patients continued to have HTN post-tx. However, despite HTN, few stopped BV due to cardiovascular events. Further education regarding HTN guidelines may be necessary and should be considered.
Virulizin induces production of IL-17E to enhance antitumor activity by recruitment of eosinophils into tumors
Authors: T. Benatar, M. Y. Cao, Y. Lee, N. Feng, X. Gu, V. Lee, H. Jin, M. Wang, S. Der, J. A. Wright, A. H. Young
Journal: Journal of Clinical Oncology (2005)

2537 Background: Virulizin (V), has demonstrated strong antitumor activity in a variety of human tumor xenograft models including skin, pancreatic, breast, ovarian and prostate cancer. V is currently undergoing a pivotal Phase III clinical trial for the treatment of advanced pancreatic cancer in combination with Gemcitabine. A significant role of macrophages and NK cells was implicated in the antitumor mechanism of V where expansion as well as increased activity of macrophages and NK cells were observed in mice treated with V. The aim of this study is to evaluate the role of the inflammatory cytokine IL-17E (IL-25) in the antitumor mechanism of V. IL-17E is a proinflammatory cytokine, which can induce a TH2 immune response, associated with eosinophil expansion and infiltration into mucosal tissues. Methods: Antitumor activity of V was assessed on human melanoma C8161 xenograft in CD-1 nude mice. Alteration of IL-17E production in sera from V-treated mice was identified by 2-D gel electrophoresis and MALDI-TOF. The level of IL-17E in the sera was also determined by ELISA. IL-17E mRNA expression was determined by quantitative real-time RT-PCR. Intracellular expression of IL-17E was examined by flow cytometric analysis. The cell surface marker CCR3 on eosinophils was analyzed by flow cytometry. Results: Cytokine IL-17E was increased in sera of V-treated mice bearing human melanoma xenograft, as shown by 2-D gel electrophoresis and ELISA. Treatment of splenocytes in vitro with V resulted in increased IL-17E mRNA expression, which peaked between 24 and 32 hours post-stimulation. Both in vitro and in vivo experiments demonstrated that B lymphocytes produce IL-17E upon V treatment. Furthermore, V treatment in vivo resulted in increased blood eosinophilia. Conclusion: In addition to activating innate immune system, V may manifest its antitumor activity through induction of IL-17E in B cells. This may lead to the recruitment of the proinflammatory cell type, eosinophils, which may function in parallel with macrophages and NK cells in mediating tumor destruction. No significant financial relationships to disclose.
Outcomes with FOLFIRINOX for locally advanced pancreatic cancer.
Authors: Brian A. Boone, Jennifer Steve, Alyssa M. Krasinskas, Amer H. Zureikat, Barry C. Lembersky, Michael K. Gibson, Ronald Stoller, Herbert J. Zeh, Nathan Bahary
Journal: Journal of Clinical Oncology (2013)

256 Background: Trials examining the use of FOLFIRINOX in metastatic pancreatic ductal adenocarcinoma demonstrate significantly higher response rates compared to gemcitabine-based regimens. These high response rates may be particularly important for patients with locally advanced pancreatic ductal adenocarcinoma (LAPD), in which there is currently limited experience with FOLFIRINOX. We examined the outcomes of patients with LAPD treated with neoadjuvant FOLFIRINOX at our high volume clinic. Methods: Retrospective review of a prospectively maintained pancreatic cancer database was used to identify patients who were recommended neoadjuvant treatment with FOLFIRINOX. Clinical outcomes were reviewed. Resectability was determined using SSO criteria. Results: Between 2/2011 and 9/2012 FOLFIRINOX was recommended for 25 patients with LAPD, 13 (52%) unresectable (UR) and 12 (48%) borderline resectable (BR). Median age was 59. 4 patients (16%) either refused treatment or were lost to follow up. 21 patients (84%) were treated with a median of 4.7 cycles (Range: 2-8). 5 patients (24%) required dose reductions secondary to toxicity. 2 patients (9%) were unable to tolerate treatment and 3 patients (14%) had disease progression on treatment. Of the remaining 16 patients, 13 patients (62%) displayed a radiologic response allowing for surgical exploration, 4 (31%) of which were initially unresectable. 6 of these patients (29%) received additional chemotherapy and/or radiation therapy prior to surgery. Peritoneal metastases were discovered at surgery in 2 (8%) patients. Of the patients who were BR, 7/8 (88%) had a R0 resection. Of the 10 UR patients, 3 (33%) underwent surgical resection, with 2 (20%) R0 resections. Overall R0 resection rate was 43%. A total of 4 patients (19%) demonstrated a major pathologic response (2 complete responses and 2 near complete responses) and 8 other patients (73%) had some pathological response. Conclusions: FOLFIRINOX alone or as part of multimodality approach is a biologically active regimen in LAPD with encouraging R0 resection rates, especially in BR LAPD. Further research is needed to determine the utility of additional chemoradiotherapy with FOLFIRINOX and to identify predictors of response in UR patients.
Sunitinib (SU) pharmacokinetic (PK)–pharmacodynamic (PD) modeling with respect to safety and efficacy endpoints in Asian patients (pts) with gastrointestinal stromal tumor (GIST) or renal cell carcinoma (RCC) in pursuit of a therapeutic window.
Authors: R. Khosravan, G. Mugundu, N. Agata, E. Ueda, T. Nishida, H. Akaza
Journal: Journal of Clinical Oncology (2011)

e15128 Background: SU is an oral multitargeted tyrosine kinase inhibitor, approved multinationally for the treatment of advanced RCC, imatinib-resistant or -intolerant GIST, and well-differentiated pancreatic neuroendocrine tumor. We explored SU PK–PD relationships with respect to safety and efficacy endpoints to determine a therapeutic window for SU in Asian pts with GIST and RCC. Methods: We analyzed pooled PK–PD data from two Japanese phase II studies in pts with GIST and RCC (N=81 combined) using NONMEM V7.0. We initially built a PK model (2-compartments with 1st order absorption and elimination) to describe SU PK data. Subsequently, different sequential semi-mechanistic or mechanism-based (i.e., transit compartments with feedback loop [TCF] or indirect response [IDR] with Emax or sigmoid Emax drug effect) PK–PD models were built and compared for selection of a PK–PD model to describe each PD endpoint; these models were internally validated by Visual Predictive Check using PsN and Xpose. Results: Key PK–PD model characteristics or parameter estimates are shown in the table below. There appeared to be great inter-pt variability in, and overlap between, the exposure-response curves for safety endpoints and that of the efficacy endpoint. Conclusions: We could not identify a therapeutic window for SU in Asian pts with GIST and RCC. SU dose modification based on individual pt safety/tolerability appears to be the best approach to ensure maximum SU plasma exposure and efficacy, consistent with the SU label recommendation. PD endpoint PK–PD model EC50 Mean (CV) ng/mL (%) γ Mean Safety Absolute neutrophil count TCF 6.91 (146) 1(F) Platelet count TCF 55.7 (27) 5.22 Lymphocyte count IDR 98.6 (NE) 3.09 LVEF IDR 1050 (180) 1(F) Diastolic blood pressure IDR 318 (44) 1(F) AST TCF 74.7 (NE) 4.66 Efficacy SLD IDR 80.1 (248) 1(F) Abbreviations: CV, coefficient of variation; EC50, SU concentration at which 50% of the maximum effect is achieved; F, fixed; γ (gamma), Hill coefficient; LVEF, left ventricular ejection fraction; NE, not estimable; SLD, sum of the largest diameters of target tumors.
An electronic chemotherapy administration safety checklist: The safe transition from paper to computer.
Authors: MiKaela M. Olsen, Monica Wilt, Barbara Van de castle, Kathy Mooney, Melanie Cohen, Elizabeth Taffe, Marie Swisher, Jackie McCready, Denise Daniel, Sharon Krumm, Allen Ray Sing Chen
Journal: Journal of Clinical Oncology (2012)

303 Background: This abstract describes the successful implementation of an electronic chemotherapy administration safety checklist and the outcomes that led to further enhancement of safe chemotherapy administration. The purpose of this abstract is to give an overview of the processes in transitioning from a paper checklist to an electronic version. Following the implementation of a paper chemotherapy administration safety checklist in 2002, this cancer center realized a significant reduction in chemotherapy errors reaching patients. The checklist became a model for many practitioners across the U.S. Our implementation of the Sunrise computerized provider order entry (CPOE) system in oncology inpatient units in 10/2009 included support for all of the 2009 ASCO/ONS chemotherapy ordering standards, and featured a two-way interface with the pharmacy system, and an electronic medication administration record. In the 12 months following its deployment, the rate of chemotherapy errors that reached the patient fell from 2.71 per 100 chemotherapy admissions using our paper system to 1.11 per 100 chemotherapy admissions using CPOE. With the advent of electronic documentation it became apparent that the paper checklist was outdated. Methods: An electronic chemotherapy checklist was implemented, replacing a paper version that had been in use for almost a decade. The proper design and implementation of the electronic version were essential to ensure that the safety achieved with the paper checklist was not compromised. After pilot testing, the checklist was implemented. Results: The electronic chemotherapy checklist was accepted by staff and resulted in a decrease in errors reaching the patient. Conclusions: The safe administration of chemotherapy is the number one priority at our cancer center. To our surprise the electronic checklist has been a welcomed addition to our armamentarium against chemotherapy errors. The checklist has enhanced independent safety checks due to required independent sign-on of the electronic system. The checklist also heightened awareness of chemotherapy safety checks, which were unchanged, leading us to believe that the paper version had become somewhat ineffective.
Endostar inhibits malignant ascites production in mice model bearing tumor ascites.
Authors: Q. Shukui
Journal: Journal of Clinical Oncology (2011)

e21014 Background: Endostar is a modified rh-endostatin expressed and purified in E.coli, an additional nine-amino acid sequence is added at the N-terminal of the protein, which improves the stability and activity of the protein. A series of studies have demonstrated that endostar strongly inhibits the growth of a variety of murine and xenotransplanted human tumors by suppressing the neovascularization. The present study was designed to investigate inhibitory effects of endostar in mice model. Methods: The mice models of tumor ascites with S180 and H22 cells by intraperitoneal inoculation were established. Model animals were randomly distributed into 4 groups with 12 mice respectively. 3 groups received different doses of endostar treatment: 4, 8, and 16 mg/kg, respectively. The control group received 0.9% normal saline.The mice were killed to collect the ascites. Then we analyzed the membrane permeability according to it.Apoptosis and cell cycle of tumor cells in the ascites fluid were detected by flow cytometry. The level of VEGF was determined by ELISA in blood serum and ascites fluid. Kaplan-Meier analysis was performed to determine animal survival time. Results: Establishment of mice model bearing tumor ascites was successful with S180 cells and H22 cells by intraperitoneal inoculation. Doses of 8, 16 mg/kg endostar could suppress volume of ascites, and the number of tumor cells and red cells in the ascites fluid (P<0.05, respectively).The different doses of endostar (dose at 4, 8 and 16mg/kg) could profoundly depress peritoneum permeability (P<0.05, respectively). The 8, 16mg/kg endostar could reduce tumor burden of abdominal cavity, and down-regulate the level of VEGF in blood serum and ascites fluid (P<0.05, respectively). Endostar induced mild apoptosis and cell cycle on S180 and H22 cells (P>0.05, respectively). And survival time of 8, 16mg/kg endostar-treated mice was longer than that of control group mice. Conclusions: Results revealed for the first time that endostar could obviously suppress ascites formation, as well as prolonging survival time of test mice bearing S180 and H22 tumor ascites. Endostar is expected to be a novel therapeutic strategy and drug for treating advanced stage cancer with malignant ascites.
An institutional analysis of gemcitabine and capecitabine for advanced biliary cancer.
Authors: Shipra Gandhi, Emmanuel M. Gabriel, Kristopher Attwood, Wen Wee Ma, Boris W. Kuvshinoff, Steven N. Hochwald, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2016)

342 Background: The results of ABC-2 trial established gemcitabine and cisplatin (gem-cis) as a standard regimen for advanced biliary cancer. Although no randomized trial has been performed with gemcitabine and capecitabine (gem-cap), this regimen has reported benefits and has been a standard treatment at our institution. We report our experience with outcomes and toxicity. Methods: This is a single institution, retrospective study from 2005-2015 of patients with advanced biliary cancer, including intra and extrahepatic cholangiocarcinoma (IHCC/EHCC) and gallbladder carcinoma (GBC). Overall survival (OS) and progression-free survival (PFS) on gem-cap were reported using standard Kaplan-Meier methods. Comparisons were made using log-rank test. Results: A total of 372 patients were identified. Of these, 227 (61.0%) had chemotherapy data at our institution. A total of 153 patients (41.1%) received gem-cap, 133/153 (86.9%) received it in first line. The majority of patients (67.4%) had metastatic disease. Twenty-seven patients (17.6%) received it as adjuvant therapy, of which 16 (10.5%) also received adjuvant radiation. Forty-four patients (33.1%) received second line of chemotherapy and 12 (9.0%) received third line. Disease sites included 48.9% IHCC, 24.0% EHCC and 27.1% GBC. Median follow-up was 45.1 months (mo). The median OS and PFS for the entire cohort were 13.0 mo (95% CI 10.7-17.4) and 8.0 mo (6.0-9.3), respectively. Patients with metastatic disease had poorer OS and PFS compared to locally advanced disease: median OS – 11.4 vs 16.3 mo (p = 0.01); median PFS – 6.9 vs 10.4 mo (p &lt; 0.001). There was no statistically significant differences in OS/PFS by disease site. Overall, 69 patients (55.6%) experienced grade 3/4 toxicity. The most common (35.7%) was hematologic toxicity (neutropenia/thrombocytopenia). Other adverse events included elevated LFT’s (9.3%) and non-hematologic events (22.5%), including fatigue (6.8%) and hand-foot syndrome (6.0%). Conclusions: Gem-cap provides a similar PFS to gem-cis based on historical comparison with ABC-2 trial. Gem-cap may offer the advantage of fewer adverse events (55.6%) compared to the 70.7% reported in ABC-2. Prospective comparison of these two regimens is warranted.