tbuckley/cabot-search huggingface dataset:
Association of histologic grade and subtypes of gastric cancer (GC) with chemoradiation response.
Authors: Nikolaos Charalampakis, Graciela M. Nogueras-Gonzalez, Xuemei Wang, Elena Elimova, Hironori Shiozaki, Roopma Wadhwa, Venkatram Planjery, Jeana Garris, Jane Elizabeth Rogers, Adarsh Hiremath, Mariela A. Blum, Jeffrey H. Lee, Manoop S. Bhutani, Brian Weston, Jeannelyn Estrella, Aurelio Matamoros, Prajnan Das, Brian D. Badgwell, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2015)

97 Background: Patients with localized gastric cancer (LGC), when treated with preoperative therapy, tend to have heterogeneous and unpredictable outcomes. Currently, no clinical variables or biomarkers can predict response. Methods: We analyzed 107 LGC patients who were treated with chemoradiation followed by surgery (trimodality therapy; TMT). Tumors were grouped into poorly (G3) or moderately (G2) differentiated and signet ring cell (SRC) or non-SRC histology. Association was made with pathologic complete response (pathCR) or &lt; pathCR. Descriptive statistics and survival analyses were utilized. Results: The majority of the patients were male (60%), had clinical stage III cancer (51%), and received chemotherapy before chemoradiation (94%). All had adenocarcinoma and most had G3 (78%) and SRC histology (58%). PathCR was noted in 18% of patients with G3 and 33% of patients with G2 (p=0.125). Overall survival (OS) was significantly shorter for G3 patients compared to G2 patients (p=0.045). Patients with SRC histology had a lower rate of pathCR than those with non-SRC (8% vs 40%, p&lt;0.001). Patients with SRC histology had a trend towards shorter OS (p=0.063). Surgical pathologic stage was independently associated with OS and recurrence-free survival (RFS) (p&lt;0.001). Conclusions: Our data suggest that histologic grade/ subtypes are associated with response to preoperative chemoradiation. Independent validation and addition of biomarkers could allow individualization of therapy of LGC patients. From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. (Supported in part by UTMDACC, and CA 138671 and CA172741 from the NCI). Dr. Nikolaos Charalampakis has been awarded a scholarship from the Hellenic Society of Medical Oncology.
The impact of compliance to oncology pathways that include G-CSF rules for use on ER visits/hospitalizations in a multistate program.
Authors: Andrew Delgado, Ted Kim, Eugene Kreys, Jim M. Koeller
Journal: Journal of Clinical Oncology (2013)

135 Background: CareFirst BCBS initiated a multistate oncology pathway program in 2008, which reduced chemotherapy and hospitalization expenditures and also increased supportive care drug utilization. This study evaluated the impact of following pathways including supportive care versus not following pathways on ER visits/hospitalizations and associated costs as a result of anemia, neutropenia, and chemotherapy-induced nausea and vomiting (CINV). Methods: The CareFirst claims database was utilized to evaluate data two years after initiation of the pathways program. Frequency of ER visits/hospitalizations for neutropenia, anemia and CINV was the primary outcome measured and was compared between compliant and noncompliant pathway utilization of granulocyte colony-stimulating factors (G-CSFs), erythropoiesis-stimulating agents (ESAs), and antiemetics, respectively. Logistic regression analyses were used to control for expenditures of ESAs, CSFs, and antiemetics in the context of compliance and the corresponding visit types. Costs associated with ER visits/hospitalizations were also compared between compliant and noncompliant pathway utilization of supportive care. Results: Overall, 46 sites with 1,586 patients were evaluated. There were a total of 12 ER visits/hospitalizations for anemia, 231 for neutropenia, and 360 for CINV. G-CSF pathway compliance resulted in a relative reduction in ER visits/hospitalizations of 67.2% (from 28.3% to 11.5%, p&lt;0.001). Logistic regression showed consistent results when controlling for costs with a 69.5% relative reduction of ER visits/hospitalizations (p&lt;0.001). A comparison of ER visits/hospitalization costs as a result of neutropenia demonstrated G-CSF pathway compliance producing an average savings of $1,173 per line of therapy (p=0.001). Analogous analyses did not demonstrate a significant relationship between ESA and antiemetic utilizations and their corresponding ER visits/hospitalizations. Conclusions: Adherence to oncology pathways, including G-CSF use rules, is associated with a significantly lower ER visits/hospitalization rates and costs associated with febrile neutropenia.
Reduction of paclitaxel neuropathy with cryotherapy.
Authors: Mary Wilkinson, Costanza Cocilovo, Hernan I. Vargas, Robert Alan Cohen, Sara Bruce, Kirsten H. Edmiston, Claudia Yvette Franco, Maria Gracia Agra, Suzanne Bayer, Afifah Khan, Lamvy Le, Parisa Saifollahi, Mary Steimer, Christopher Szeremeta, John F. Deeken
Journal: Journal of Clinical Oncology (2016)

124 Background: Chemotherapy induced peripheral neuropathy (CIPN) is a common and potentially debilitating side effect of taxanes. Prior studies indicate weekly paclitaxel results in grade 2 or higher neuropathy in 25% of patients. Patients may experience persistent pain that impacts quality of life. Currently, there is little data that exists on effective therapies for prevention of paclitaxel neuropathy. This study investigates the efficacy and safety of cryotherapy for the prevention of paclitaxel-induced peripheral neuropathy. Methods: This is a single arm, phase II study of the effects of cryotherapy for breast cancer patients undergoing 12 cycles of weekly paclitaxel. Cryotherapy was administered by hypothermia mitts and slippers to patients’ hands and feet during, and 15 minutes before and after paclitaxel treatments. Neurologic assessments and neuropathy questionnaires were evaluated at baseline, every 4 cycles during treatment, and every 6 months follow up for two years. The primary objective is to assess if cryotherapy can decrease the rate of peripheral neuropathy. The primary efficacy endpoint is the rate of neuropathy in patients undergoing weekly paclitaxel treatments. Results: Between November 2014 and June 2015, 41 patients were enrolled in the study. Of 39 evaluable patients, 19 (48.7%) were without neurologic toxicity. 19 (48.7%) had grade 1 toxicity, paresthesia but without pain. Only one patient (2.6%) had grade 2 toxicity. Cryotherapy treatment was well tolerated; one patient could not participate due to cold intolerance. Conclusions: Cryotherapy reduced the incidence of pain and grade 2 or higher sensory neuropathy in patients receiving weekly paclitaxel. Clinical trial information: NCT02230319. [Table: see text]
A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and bevacizumab (bev) as a first-line therapy for patients with metastatic colorectal cancer.
Authors: Yasushi Sato, Hiroyuki Ohnuma, Masahiro Hirakawa, Minoru Takahashi, Takahiro Osuga, Kohichi Takada, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Kenji Okita, Tomohisa Furuhata, Koichi Hirata, Junji Kato
Journal: Journal of Clinical Oncology (2014)

612 Background: In a recent study by Loupakis, F. et al. (ASCO-GI 2013), a FOLFOXIRI and bevacizumab regimen showed promising activity and conversion rate in patients (pts) with metastatic colorectal cancer (mCRC). In order to evaluate a treatment regimen that was easier to administer, we conducted a dose-escalation study to determine the recommended dose (RD) of irinotecan (IRI) in combination with oxaliplatin and capecitabine and bevacizumab (XELOXIRI/bev) in pts with mCRC. Methods: Pts were eligible if they had mCRC (liver and/or other metastases), ECOG PS 0-1, were either negative or heterozygous for UGT1A1*6 or UGT1A1*28 and were not pretreated for metastatic disease. Treatment consisted of oxaliplatin (100 mg/m 2 day 1), capecitabine (1700 mg/m 2 /day from day 2 to 15), IRI (100,120,150 mg/m 2 for dose levels 1, 2, or 3, day 1) and bev (7.5 mg/kg, day 1), repeated every 3 weeks. The dose of IRI was escalated if dose limiting toxicities (DLT) were absent in the first three pts per cohort, or if &lt;2 DLTs were observed in six pts. If the MTD was not reached at the planned dose levels, the RD of IRI was defined as 150mg/m 2 , which is the maximum dosage approved for use in Japan. Results: 12 pts (F/M: 4/8, median age: 58 years, PS 0/1: 11/1) received a median of 6 cycles of therapy (range 2-12). The DLT was grade 4 neutropenia, which was observed in 1 of 6 pts at dose level 2. MTD was not reached at dose level 3. Therefore, the RD of IRI was defined as 150 mg/m 2 . Most common grade ≥ 3 toxicities were neutropenia (58.3%), anemia (16.6 %), diarrhea (8.3%), and febrile neutropenia (8.3 %). The response rate was 83.3%(95% CI 60-89), including 1 CR, 9 PRs. The disease control rate was 100%(95% CI 80-100). At a median follow-up of 8 months, median PFS was 15 months and median OS was not yet reached. Conclusions: XELOXIRI/bev is a feasible regimen; neutropenia was the DLT; recommended dose of IRI is 150 mg/m². The observed response rate of 83.3% is very promising and warrants further investigation. Clinical trial information: UMIN000005440.
FOLFIRINOX and gemcitabine/nab-paclitaxel efficacy in the treatment of locally advanced unresectable pancreatic adenocarcinoma.
Authors: Filip Bednar, Lee Mayer Ocuin, Jennifer Steve, Mazen S Zenati, Sharon Winters, Melissa Ellen Hogg, Nathan Bahary, Herbert J. Zeh, Amer H. Zureikat
Journal: Journal of Clinical Oncology (2016)

399 Background: Locally advanced (LA) unresectable pancreatic adenocarcinoma (PDA) historically portends a poor prognosis with a median OS of 9-11 months. Recently, two multi-drug regimens – FOLFIRINOX and gemcitabine/nab-paclitaxel – have proven effective in the metastatic setting. We hypothesized that use of these regimens in the LA setting may improve survival. Methods: A retrospective review of a single institution’s cancer registry of all consecutive LA (unresectable) PDA patients between 2010 and 2014 was performed. LA status was verified by review of the triphasic, pancreas protocol CT scan at diagnosis using the 2015 NCCN criteria for resectability. Patients were divided into 4 groups: Group 1 = no therapy, Group 2 = “old” gemcitabine or 5-FU-based chemotherapy (CTX), Group 3 = “new” CTX (FOLFIRINOX and/or Gem/nab-paclitaxel), and Group 4 = resection after downstaging. Demographic, tumor related variables, and treatment outcomes were analyzed. Results: LA disease was verified in 107 consecutive patients. Median age was 69 years (range 36-92) and 50.5% were male. Median follow-up was 13.2 months (range 0.6-60.4). Median OS for Groups 1 (n=15), 2 (n=24), 3 (n=49), 4 (n=19) was 1.4, 11, 17.3, and 32 months respectively (p&lt;0.001). On Cox multivariate regression (adjusted for age, sex, anatomic variables, and CA19-9 level at diagnosis), radiation (HR 0.44, p=0.003), older CTX (HR 0.16, p=0.007), newer CTX (HR 0.10, p=0.001), use of 2 or more lines of CTX (HR 0.16, p=0.022), CA19-9 decrease by &gt;50% with any line of therapy (HR 0.31, p&lt;0.001), and surgery (HR 0.28, p=0.002) were all significant predictors of OS in this cohort. On multivariate analysis between groups 2 and 3, newer CTX compared to older CTX (HR 0.490, p=0.02) and radiation (HR 0.510, p=0.015) provided an OS benefit. Conclusions: Compared to older CTX regimens, FOLFIRINOX and Gemcitabine/nab-paclitaxel improve survival in verified LA PDA patients. For the subset that ultimately undergoes resection, survival outcomes rival those of historically published resectable cohorts.
Incidence of reduced penis size among men with recurrent prostate cancer previously treated with surgery, radiation plus androgen deprivation, or radiation alone.
Authors: Arti Parekh, Ming-Hui Chen, Karen Elizabeth Hoffman, Toni K. Choueiri, Jim C. Hu, Charles L. Bennett, Michael W. Kattan, A. Oliver Sartor, Karen Stein, Anthony Victor D'Amico, Paul Linh Nguyen
Journal: Journal of Clinical Oncology (2012)

38 Background: The relative incidence of reduced penis size across prostate cancer treatment modalities is not well-known. Methods: The incidence of physician-reported patient complaints about reduced penis size was calculated for 948 men in the COMPARE registry who experienced PSA failure and were assessed a median of 5.45 (2.6-8.9 IQ range) years after prostatectomy or radiation (RT) consisting of either external beam or brachytherapy. Multivariable logistic regression was used to determine factors associated with poorer sexual function and incontinence. Results: Of 948 men, 25 (2.63%) complained of a reduced penis size. The incidence of reduced penis size by treatment was: surgery (19/510=3.73%), RT plus androgen deprivation therapy (ADT) (6/225=2.67%), RT without ADT (0/213=0%). Surgery (p=0.004) and RT+ADT (p=0.016) had significantly more short penis complaints than RT alone. Rates of shortened penis for surgery and for RT+ADT were similar (p=0.47). On multivariable analysis adjusting for age and treatment type, short penis was associated with poorer sexual function (Odds ratio: 2.430, 95% CI: 1.046-5.643) (p=0.0389) and more incontinence (Odds ratio: 4.671, 95% CI: 1.985-10.994) (p=0.0004). Conclusions: Complaints about reduced penis size were more common with RT+ADT or surgery than with RT alone, and were associated with poorer sexual function and incontinence issues.
Autocrine Loop Involving IL-6 Family Member LIF, LIF Receptor, and STAT4 Drives Sustained Fibroblast Production of Inflammatory Mediators
Authors: Hung N. Nguyen, Erika H. Noss, Fumitaka Mizoguchi, Christine Huppertz, Kevin S. Wei, Gerald F.M. Watts, Michael B. Brenner
Journal: Immunity (2017)
Final result of a phase I study of combination of pasireotide (SOM 230) LAR plus gemcitabine in metastatic pancreatic cancer (MPC).
Authors: Yaman Suleiman, Gregory M. Springett, Erin M. Siegel, David Shibata, William J. Fulp, Richard D. Kim
Journal: Journal of Clinical Oncology (2014)

277 Background: Pasireotide is a cyclohexapeptide engineered to bind to multiple somatostatin (SST) receptor subtypes (SST 1, 2, 3, and 5) to mimic the action of natural somatostatin with 40-times higher affinity for SST1 and SST5 and 5-times higher affinity for SST3 compared to octreotide and is potent inhibitor of insulin-like growth factor-1 (IGF-1). SST receptors and IGF receptors are highly expressed in pancreatic cancer, therefore potentially making it a valuable target. Methods: A 3+3 dose escalation design was used; patients with previously untreated MPC were eligible for the trial. Patients received GEM 1000 mg/m 2 (30-min, once-weekly IV infusion for 3 out of 4 weeks) and SOM 230 LAR according to dose escalation. Two dose levels were planned, 40mg IM and 60 mg IM once a month. Cohort was expanded to 10 more patients at the highest tested dose to further access safety and efficacy. IGF-1, IGFBP (insulin-like growth factor binding protein)-1, and IGFBP-3 were measured at baseline and with each restaging. Results: 20 patients enrolled with this study were treated and 16 patients (median age 65.5 years; male/female 6:10) were evaluable for safety and efficacy. No dose limiting toxicities were observed with the two used doses, therefore cohort at 60mg was expanded to 10 patients to assess efficacy. 12 % (2/16) of patients had partial responses (PR), 56% (9/16) had stable disease (SD) as best response. Median PFS was 4.1 months (range 1 to 16 months) and median overall survival was 6.8 months. Most common grade 3 or 4 toxicities were hyperglycemia (n=5), increased bilirubin (n=2), neutropenia (n=1), thrombocytopenia (n=1) and fatigue (n=1). Median baseline IGF-1 level was lower in Pts with stable disease than in progressive disease (63 vs.71 ng/mL), the median drop in the level of IGF-1 between the first cycle and the last cycle was more prominent in the stable disease than progressive disease (16 vs. 28 ng/mL). Conclusions: Pasireotide in combination with gemcitabine was well-tolerated. The disease control rate (56% SD + 12% PR) in patients with MPC. Baseline IGF-1 level may potentially be a prognostic and predictive biomarker for pasireotide. These results are promising and warrant further evaluation. Clinical trial information: NCT01385956.
A phase II trial of 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) chemotherapy plus bevacizumab (bev) for patients (pts) with unresectable stage IV colon cancer and a synchronous asymptomatic primary tumor: Updated results of NSABP C-10 with definitive survival analysis.
Authors: Laurence E. McCahill, Greg Yothers, Saima Sharif, Nicholas J. Petrelli, Samia H. Lopa, Michael J. O'Connell, Norman Wolmark
Journal: Journal of Clinical Oncology (2013)

468 Background: Surgical resection of asymptomatic primary colon tumor for pts presenting with synchronous yet unresectable metastatic disease is controversial. We published results for the primary endpoint in JCO in September 2012. Here we update the primary endpoint and present definitive survival results. Methods: Eligible pts had ECOG Performance 0 or 1, an asymptomatic colon tumor and unresectable distant metastases. Primary endpoint (PE) was major morbidity, defined as surgical resection or death related to the intact primary tumor. Major morbidity rate of 25% was considered acceptable and the trial had 85% power to rule out a rate of 40%. Secondary endpoints were overall survival and morbidity related to the intact primary requiring hospitalization, transfusion, or interventional procedure. Results: Between March 2006-June 2009, 90 pts were registered and 86 eligible pts with follow-up comprise this analysis. 52% were female and 47% were age 60+. Median follow-up was 61.5 mos. There were 15 (17.4%) major morbidity events, 12 (14.0%) required surgery: obstruction (9), perforation (2), and pain (1). Three (3.5%) resulted in pt death: perforation (2), obstruction (1). Cumulative incidence of major morbidity at 42 mos was 17.7% (95% CI 9.5-26.0%). Fourteen other primary tumor resections were performed: attempted cure (11), other reasons (3). There were 6 secondary endpoint events: 4 obstructions (2 required stents, 2 resolved with conservative management), 2 pts with suspected perforation required percutaneous drainage (1) and hospitalization and antibiotics (1). Median survival was 18.3 mos (95% CI 15.2-24.2). Two year OS rate was 38.7% and 3 year OS rate was 15.1%. Conclusions: The primary endpoint holds with the updated analysis justifying observation for asymptomatic primary colon cancers even in patients with a good clinical response of distant metastases. Clinical trial information: NCT 00321828.
A pilot trial of itraconazole pharmacokinetics in patients with metastatic breast cancer.
Authors: F. O. Ademuyiwa, Q. Zhao, S. M. Perkins, N. Gebregziabher, D. R. Jones, L. G. Vaughn, G. W. Sledge, K. Miller
Journal: Journal of Clinical Oncology (2011)

e13565 Background: Preclinical studies show that itraconazole (ITRA) has inhibitory activity against human umbilical vein endothelial cells. It also decreases angiogenesis with 67.5% reduction in new blood vessel formation in ITRA-treated mice vs. controls. The aim of this study is to determine the pharmacokinetics (PK) of ITRA in patients with metastatic breast cancer (MBC) and correlate measures of angiogenesis with plasma levels of the drug and its metabolite hydroxyitraconazole. Methods: ITRA was administered orally at 200mg daily to patients with MBC. A cycle consists of 28 days. Plasma levels of ITRA and hydroxyitraconazole were obtained at 2 and 4 weeks for PK. Plasma VEGF-A and TSP-1, serum bFGF and PlGF levels were obtained at baseline, 2, and 4 weeks. Spearman correlations (rs) of angiogenesis factors with plasma levels of ITRA and hydroxyitraconazole were computed. Toxicities, OS, TTP were determined. Results: 14 patients were enrolled, median age 62.5, with 13 being evaluable. 8 were hormone receptor-positive; 1 was HER2-positive. Median follow-up was 13.7 months. Median number of cycles was 2. Frequent AEs were fatigue (30.8%), anorexia (23.1%), insomnia (23.1%). Gr 3/4 toxicity was observed in only 1 patient (fatigue, insomnia, nausea/vomiting, dyspnea, hemorrhage, and pain). Median ITRA levels at 2 and 4 weeks were 181 and 202 ng/mL. Median hydroxyitraconazole levels were 331.5 and 337 ng/mL. Median bFGF and PlGF levels decreased with administration of ITRA from baseline to weeks 2 and 4. bFGF displayed high correlations with ITRA and hydroxyitraconazole at weeks 2 and 4 although not statistically significant (rs= -0.54 to -0.70). Plasma TSP-1 increased at weeks 2 and 4. VEGF-A levels increased from baseline to week 2, but decreased with drug administration during weeks 2 to 4. PlGF, TSP-1, VEGF-A did not correlate with drug levels. 1 patient had a PR, 3 SD, and 9 PD. Estimated TTP and OS were 1.8 and 19.3 months respectively. Conclusions: This is the first study evaluating PK of ITRA and effects on angiogenesis in MBC. Whilst reductions in pro-angiogenic factors and increases in TSP-1 (angiogenesis inhibitor) were observed with ITRA administration, our pilot study suggests a lack of correlation with drug or metabolite levels.
The NSG – Human CLL Xenograft Model Recapitulates the Human Lymph Node Microenvironment in Regards to B-Cell Activation and Tumor Proliferation
Authors: Xiameng Sun, Sarah E. M. Herman, Matthew M. Hsieh, John F. Tisdale, Jichun Chen, Georg Aue, Patricia Perez-Galan, Adrian Wiestner
Journal: Blood (2011)
Efficacy and safety of metronomic chemotherapy with all-oral combination of low-dose etoposide/capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes.
Authors: Yan Wei
Journal: Journal of Clinical Oncology (2012)

115 Background: The purpose of this study is to determine the efficacy and safety of metronomic chemotherapy with all-oral combination of low-dose etoposide/capecitabine in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and/or taxanes. Methods: From June 2008 to April 2012, 22 women with MBC were enrolled and 16 patients were evaluable for toxicity and response. Treatment consisted of capecitabine (1,400 mg/m 2 daily, taken in 2 oral doses) on days 1-14 and oral etoposide ( 30 mg/m 2 daily ) on days 1-7 . Cycles were repeated every 3 weeks unless disease progression or unacceptable toxicity occurred or patient consent was withdrawn. The primary endpoint was clinical benefit rate (CR + PR + SD≥24 weeks); secondary endpoint was toxicity and time to progression (TTP). Tumor response was evaluated by RECIST criteria, and adverse events were evaluated by NCI-CTC AE v3.0. Results: Sixteen patients were included and received 145 cycles of chemotherapy, with a median of 7 cycles (range, 2-26 cycles). One of the 16 patients had partial response (PR 6.25%), 10 showed stable disease (SD 62.5%) and 5 had progression of disease (PD 31.25%), with a clinical benefit rate of 50% (CR + PR + SD≥24 weeks). Median TTP was 5.0 months (range, 1.5-20 months), and mean TTP was 6.06 months. Adverse effects were mild, and the main adverse effects were leucopenia (13%) and fatigue (13%). All patients are survival till now. Conclusions: An all-oral combination of low-dose etoposide plus capecitabine is a new regimen and has showed effective in treating MBC patients and can be well tolerated. It’s very economic compared with most other schedules today. It is worthy of further study on a large scale, especially in the developing countries.