tbuckley/cabot-search huggingface dataset:
Interim safety analysis from a randomized, open-label, multicenter, phase III trial of capecitabine plus oxaliplatin (XELOX) versus capecitabine (X) as first-line chemotherapy in elderly patients with advanced gastric cancer (AGC).
Authors: In Gyu Hwang, Jung Hun Kang, Soonil Lee, Hyo Rak Lee, Hui Young Lee, Jun Ho Ji, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang
Journal: Journal of Clinical Oncology (2014)

158 Background: While combination chemotherapy involving fluoropyrimidines and platinum is currently considered a standard regimen in AGC, there has been a price to pay in terms of toxicity. Since the main goal of treatment in AGC remains palliation, the current multi-center phase III trial compares efficacy and safety of XELOX combination with those of X monotherapy in elderly patients with AGC. Methods: AGC Patients aged 70 years or older were randomized 1:1 to receive X (capecitabine 1000 mg/m2 bid po on D1-D14) or XELOX (capecitabine 1000 mg/m2 bid po on D1-D14 plus oxaliplatin 110 mg/m2 iv on D1). Treatment was repeated every 21 days until disease progression, unacceptable toxicity, or patient’s refusal. Primary endpoint was overall survival, and the target sample size was 200 eligible patients. This interim safety analysis contains toxicity data from the first 27 randomized patients. Results: Among the 27 patients (X: 13, XELOX 14), median age was 77 (range, 70-84) years and 24 patients had symptomatic (ECOG PS 1-2) disease. The arms of the study were balanced with respect to baseline characteristics. No treatment-related serious adverse events (SAEs) or unexpected toxicities were observed. The most frequent toxicities were anorexia, fatigue, anemia, and hand-foot skin reactions. Fatigue and sensory neuropathy were more common in XELOX than X patients. QOL data showed no significant differences between the two arms. Conclusions: Our data indicate that the addition of oxaliplatin does not add to the toxicity of single agent capecitabine as first-line chemotherapy in elderly (age ≥70 years) AGC patients. The accrual is currently ongoing (ClinicalTrials.gov, NCT01470742). Clinical trial information: NCT01470742.
The Spindle Checkpoint Protein BubR1 Is Differentially Expressed in the Lymphatic and Myeloid Lineage and Is a Determinator of Response to Spindle Poisons
Authors: Dominik Schnerch, Marie Follo, Andrea Schmidts, Julika Krohs, Julia Felthaus, Monika Engelhardt, Ralph Wäsch
Journal: Blood (2011)
Response to vinorelbine (VNB) as first-line chemotherapy in elderly patients with hormone-refractory prostate cancer (HRPC)
Authors: J. Cervera Grau Sr., G. Esquerdo Galiana, M. Romero Nieto, S. Macia Escalante, A. Juarez Marroqui, C. Llorca Ferrandiz
Journal: Journal of Clinical Oncology (2008)

16140 Background: No consensus exists regarding further therapy for the management of hormone-refractory prostate cancer in elderly patients. The efficacy and tolerability of Vinorelbine as single agent has not been assed. To provide recommendations for further investigations we analized retrospectively our series of elderly patients. Methods: From 2005 to 2007,16 elderly HRPC patients were treated with VNB 60 mg/m2 orally d1–8/21d Median age 77,6 years; PS 0–2 100%. Results: Median courses 4,7; Median TTP 6m.;In a follow-up from 7m to 19 m a Median GS 13 m has been reported. Common toxicity; Nausea 31.25%, Aenemia 18.75%, diarrhea 18.75% was reported.Overal Response was observed in 37.5%; stable disease in 18.75%. Overal control disease 56.25%. Conclusions: Although our follow-up is short (7–19 m), we have observed a good disease control (56.25%) with a good orally VNB tolerability in ederly patients. Oral VNB could be an option in this patients, more dates will be necessary. No significant financial relationships to disclose.
Interleukin-2 (IL-2) chrono-infusion (CHI) in metastatic renal cell carcinoma (mRCC): A phase I/II study.
Authors: Giovanni Lo Re, Davide Adriano Santeufemia, Oliviero Lenardon, Renato Talamini, Alessandro Del Conte, Wally Marus, Gianluigi Nicolosi, Paolo Mancinelli, Salvatore Tumolo, Antonio Garbeglio
Journal: Journal of Clinical Oncology (2012)

423 Background: The soprachiasmatic nucleus represents the pacemaker coordinating circadian rhythm. Its dysregulation in neoplastic patients (pts) can be an important inducer/promoter of cancer progression. It is a potential mediator of cancer immunosuppressive effect and quality of life (QoL) impairment. CHI allows concentration of time active treatment with possible impact on QoL and immune and hormone set-up. Aim of this study was to evaluate feasibility, dose limiting toxicity and activity of CHI IL-2 in mRCC. Methods: 22 pts were enrolled, 14 were naive and 8 pretreated (chemo/immunotherapy in 6 and targeted in 6). M/F ratio was 16/6, median age 68 y. IL-2 CHI was administered iv in 8 h (peak 1 am, 9 am, 5 pm) from 2 MUI/m2 with escalated dose ( Fibonacci scale) x 3 days/q 2 wks for 4 cycles. Four maintenance cycles were performed in responsive/stable pts. Results: from January 2005 to July 2009, out of 22 pts, 3 were treated onto each Le (I-V ) and 7 in the VI. G3-4 toxicity was reported in four pts (hypotension in 2, renal in 2 and diarrhoea in 1) on the VI Le ( DLT 18,6 MUI/m2). Response: 1 CR, 2 PR, 9 SD, 10 PD. ORR was 25%%. DCR on overall/ good-intermediate group (MSKCC) was 54%/69%. Median PFS and OS were 4,5 and 14,5 mos respectively. In a univariate analysis dose Le (4-6 vs. 1-3), PS (0 vs 1-2), gender (M vs F) and cD3, cD4, cD8 count (gain vs drop) were statistically significant for OS. In a univariate analysis age (&lt; 65 y vs. &gt;65y), Motzer score (0-1-2 vs 3) increase/reduction of cD19, cD16, HLA-DR, cD4/cD8, increase/reduction of prolactine, reduction/increase of ACTH-Cortisol showed a trend of survival improvement. Conclusions: IL-2 CHI aappeared safe in a standard care unit, moderately toxic and active in mRCC. Phase 2 study with dose Le V is now ongoing.
Validation of the Decipher prostate cancer classifier in intermediate to high-risk men treated with radical prostatectomy but without additional therapy upon PSA rise.
Authors: Ashley Ross, Kasra Yousefi, Bruce J. Trock, Voleak Choeurng, Lucia L.C. Lam, Helen L. Fedor, Mercedeh Ghadessi, Christine Buerki, Stephanie Glavaris, Debasish Sundi, Jeffrey Tosoian, Misop Han, Elizabeth B. Humphreys, Alan W. Partin, George J. Netto, Elai Davicioni, Edward M. Schaeffer
Journal: Journal of Clinical Oncology (2015)

173 Background: Radical prostatectomy (RP) is a primary treatment option for men with intermediate and high risk prostate cancer. Though many will be effectively cured with local therapy alone, these men are by definition at higher risk of adverse pathologic findings and clinical disease recurrence. The Decipher test has been previously shown to predict metastatic progression in cohorts that included adjuvant and salvage therapy after RP. Here we evaluate Decipher in a natural history cohort of at risk men who received no additional treatment until the time of metastatic progression. Methods: Men with NCCN intermediate or high risk localized prostate cancer treated with RP at the Johns Hopkins Medical Institute (1992-2010) with at least 5 years of post-operative follow up were identified. Only men with initial undetectable PSA after surgery and who received no therapy prior to metastasis detection were included (n=765). A case-cohort design was used to randomly sample the cohort. The highest Gleason grade cancer tissue was used for RNA extraction and Decipher genomic classifier (GC) scores were calculated with a locked 22-biomarker signature and algorithm. Results: GC results were obtained for 260 patients, 28% had positive margins, 77% had EPE, 28% had SVI, 20% had lymph node invasion and 36% had Gleason ≥8 disease. Median follow up was 9 (IQR 6-12) years and at 15 years post RP the cumulative incidence of BCR, metastasis and prostate cancer specific death was 38%, 21% and 9%. Median GC score was 0.34 (IQR: 0.22-0.52) and was significantly higher among men experiencing metastatic progression during follow up (0.47 vs 0.28 respectively p&lt;0.001). In UVA and MVA (adjusting for clinical covariates), GC had an HR of 1.48 (95% CI: 1.30-1.69, p&lt;0.001) and 1.37 (95% CI: 1.21-1.55, p&lt;0.001) per 10% increase, respectively. Conclusions: The majority of the men in this study had excellent long-term outcomes with surgery alone. Elevated Decipher scores correlated with metastatic events, independent of clinical risk factors. Use of Decipher may allow for selection of candidates for immediate vs. delayed adjuvant or salvage therapy following prostatectomy.
Does Gleason score (GS) predict efficacy of abiraterone acetate (AA) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)? An analysis of AA phase 3 trials.
Authors: Karim Fizazi, Thomas W. Flaig, Carsten-Henning Ohlmann, Howard I. Scher, Johann Sebastian De Bono, Dana E. Rathkopf, Charles J. Ryan, Thian San Kheoh, Jinhui Li, Mary Beth Todd, Thomas W. Griffin, Arturo Molina, Michael Stöckle
Journal: Journal of Clinical Oncology (2014)

20 Background: GS is strongly prognostic in localized PC but is less so in mCRPC (Halabi S, J Clin Oncol 2003; Armstrong AJ, Eur J Cancer 2010). Pts with high-risk localized PC and high GS who undergo radiation therapy benefit from long-term androgen deprivation therapy (Horwitz EM, J Clin Oncol 2008). In mCRPC, the impact of GS at initial diagnosis on response to AA therapy is unknown. We retrospectively evaluated efficacy outcomes in pts with mCRPC treated with AA plus prednisone (P) vs P alone in pivotal studies COU-AA-301 (post-docetaxel) and COU-AA-302 (chemo-naive) by GS (≥ 8 or &lt; 8). Methods: 1,048 pts in COU-AA-301 and 996 in COU-AA-302 with mCRPC treated with AA 1 g + P 5 mg po BID or placebo + P had GS data at diagnosis. Efficacy end points evaluated: overall survival (OS), radiographic progression free survival (rPFS), and time to prostate-specific antigen progression (TTPP) (de Bono JS, NEJM 2011; Fizazi K, Lancet Oncol 2012; Ryan CR, NEJM 2013). Distributions and medians were estimated by the Kaplan-Meier method, and hazard ratio (HR) and 95% confidence interval were estimated by the Cox model. Results: Proportion of pts with GS ≥ 8 and GS &lt; 8 was similar across treatment groups and studies. Outcomes by GS are summarized in the Table. Conclusions: GS (≥ 8 or &lt; 8) at initial diagnosis was not predictive of treatment benefit of AA + P vs P alone in post-docetaxel and chemo-naïve pts with mCRPC, with both groups benefiting. In this era of novel androgen signaling targeted agents, GS may not be relevant in predicting efficacy with AA for pts with mCRPC. Clinical trial information: NCT00638690, NCT00887198. [Table: see text]
Correction
Authors: Norman Kneteman, Amy Weiner, John O'connell, Marc Collett, Tiejun Gao, Lea Aukerman, Rosemary Kovelsky, Zhi-Je Ni, Qing Zhu, Ahmad Hashash, Janine Kline, Belinda Hsi, Daniel Schiller, Donna Douglas, D Tyrrell, David Mercer
Journal: Hepatology (2006)

by Kneteman et al.
Associations between county-level surgeon density and colorectal cancer (CRC) mortality.
Authors: J. S. Albarrak, M. Y. Ho, W. Y. Cheung
Journal: Journal of Clinical Oncology (2011)

6018 Background: Strong associations between surgical procedure volumes and patient outcomes have been consistently observed for many types of cancers. Whether surgeon density in a population has a similar impact on cancer outcomes is unclear. Our aims were to 1) explore the effect of US county-level surgeon density on CRC mortality and on annual changes in death, 2) compare the relative importance of colorectal surgeon (CS) versus general surgeon (GS) density on these CRC outcomes and 3) identify other county characteristics associated with decreased mortality. Methods: Using county-level data from the Area Resource File, US Census and National Cancer Institute, we developed multivariate regression models to determine the effect of a) CS and b) GS on overall CRC mortality as well as on changes in death between 2002 and 2006, while controlling for CRC incidence, county demographics and other socioeconomic factors. Results: A total of 1,767 US counties were included: mean CRC incidence and death rates were 64.9 and 19.9 per 100,000 people; 45% were metropolitan and 55% were rural counties; mean CS and GS densities were 1.3 and 4.1 per 100,000 people, respectively. When compared to counties with no CS and no GS, those with at least of one of these surgeons had a statistically significant decrease in CRC-specific mortality (beta coefficients -0.35 and -0.2 for CS and GS, respectively; p=0.014). Increasing the county-level density of surgeons improved outcomes, but increasing it beyond 6 CS or 14 GS per 100,000 people did not continue to result in significant reductions in CRC mortality. Similar associations between surgeon density and annual changes in CRC-related death were observed. Counties with a high proportion of Medicare enrollees also showed increased CRC mortality. Conclusions: The presence of CS and GS at the county level is each associated with lower mortality from CRC. However, there appears to be a ceiling effect at which point further increases in their density do not produce continued improvements in CRC outcomes. A balanced strategy of allocating healthcare resources and distributing the surgical workforce evenly across all counties will likely offer the most substantial population-based improvements in CRC mortality.
Practice pattern for patients receiving secondline treatment for non-small cell lung cancer (NSCLC) with erlotinib in the community setting
Authors: L. J. Blakely, L. S. Schwartzberg, E. J. Stepanski, C. Reyes, D. Kapur, P. W. Cobb, F. M. Schnell, M. S. Walker
Journal: Journal of Clinical Oncology (2008)

19102 Background. Treatment of patients (pts) in clinical practice may vary from that on clinical trials. The objectives of this study were to characterize the clinical course of treatment, the rationale for treatment changes, and symptom burden for patients with NSCLC treated with erlotinib in community oncology clinics. Methods. A retrospective chart review was conducted at 4 community oncology sites in the US. Data were collected on 45 pts who received single agent erlotinib as either 2nd or 3rd line therapy for NSCLC between November 2004 and June 2007. Results. The sample was 44% female, 84% Caucasian (16% African American), with mean age of 66.7 (± 9.2). The mean # of cycles of erlotinib administered was 5.9 (± 6.4; range < 1–23). The mean # of clinic visits was 9.1 (± 9.0; range 1–43). Ten pts (22%) were hospitalized during erlotinib therapy, and 4 had multiple hospitalizations. 11 pts (24%) had a dose reduction while on erlotinib, and 13 (29%) had a dose delay. The most common reasons for dose reduction and delay were rash, diarrhea, and fatigue.32 pts (71%) received a carbo/taxane combination as first line therapy. The most common reasons for treatment discontinuation were: disease progression (53%), death (22%) and toxicity (11%; primarily appetite and GI symptoms). Conclusions. These results show that community practice patterns for use of erlotinib are generally consistent with data from the clinical trials literature. Older age and higher rate of dose reductions in pts receiving 2nd vs 3rd line treatment may reflect a selection of pts into the 2nd line group with worse performance status who were poor candidates for additional chemo. 2nd Line (n=26) 3rd line (n=19) p value Age 68.9 ± 9.5 63.7 ± 8.1 .058 # of cycles 7.2 ± 7.8 4.2 ± 3.5 .101 # of clinic visits 10.8 6.8 >.2 % Medicare/ Medicaid 85% 53% .043 % with dose reduction 35% 11% .086 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc.
Radiofrequency ablation for pulmonary metastases from esophageal squamous cell carcinoma.
Authors: Hironobu Shigaki, Keisuke Kosumi, Ryuma Tokunaga, Kazuto Harada, Junji Kurashige, Masaaki Iwatsuki, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba
Journal: Journal of Clinical Oncology (2016)

138 Background: Radiofrequency ablation (RFA) is increasingly being used for the treatment of intrathoracic malignancies. Although RFA has been found to be promising in the treatment of lung metastases from some types of neoplasms, little is known concerning its clinical significance in the treatment of pulmonary metastasis from esophageal squamous cell carcinoma (ESCC). This retrospective study evaluated the feasibility, safety, and effectiveness of computed tomography-guided RFA for pulmonary metastasis from ESCC. Methods: Of 322 patients with ESCC underwent esophagectomy at Kumamoto University Hospital between January 2007 and May 2015, 23 cases had pulmonary recurrence. Selection criteria for CT-guided RFA for pulmonary metastasis were as follows: (i) there were no distant metastases except for pulmonary lesions, when there were extrapulmonary recurrences that had to be controlled by additional therapies; (ii) there were up to three pulmonary tumors; (iii) the number of pulmonary tumors did not increase over a certain period while receiving pre-RFA chemotherapy; (iv) the metastatic lesions were not adjacent to major pulmonary vessels, major bronchi, or the heart. 17 patients who underwent CT-guided RFA for metachronous pulmonary metastasis from ESCC were included in this study. Results: Correct placement of the ablation device into the target tumor proved to be feasible in all tumors (100%). The mean visual analog scale score, with values that ranged from 0 (no pain) to 10 (worst pain possible), was 1. This suggested that this procedure was well tolerated. No procedure-related deaths occurred. A pneumothorax needing drainage was a major complication in two patients. 6 patients died of recurrent disease. The predicted 1- and 2-year overall survival rates after lung RFA were 78.8% and 46.7%, respectively. Conclusions: Percutaneous computed tomography-guided RFA yielded relatively high levels of local control in patients with pulmonary metastases from ESCC and was associated with an acceptable level of complications. It was concluded that a prospective study will be necessary to evaluate the effectiveness of a combination of systemic therapy and RFA for ESCC lung metastases.
The role of NF-κB pathway in cancer inflammation of esophageal squamous carcinoma.
Authors: Ching Tzao, Li-Yuan Cheng, Chien-Chih Chang, Guang-Huan Sun
Journal: Journal of Clinical Oncology (2013)

42 Background: Chronic inflammation plays an important role in tumorigenesis and tumor progression in human cancers. We aim to investigate the role of NF-kB in cancer inflammation of esophageal squamous cell carcinoma (ESCC). Methods: To generate M2-polarized macrophages, cells of human U937 monocyte cell line were treated with phorbol myristate acetate (PMA, 50 ng/ml) for 6 hours, and then cultured with PMA plus Th2 cytokines, IL-4 (20 ng/ml) and IL-13 (20 ng/ml), for another 18 hours. M2 phenotype was verified by flow cytometry and by cytokine profiling using enzyme-linked immunosorbent assay (ELISA). After co-culture with M2 macrophages, transcription nuclear factor-kB (NF-kB) activity was measured using quantitative polymerase chain reaction (Q-PCR), followed by reconfirmation with Western blot analysis for IkBα in KYSE-170 and -510 ESCC cell lines (kindly provided by Dr. Yutaka Shimada at Kyoto University, Japan). A selective inhibitor to NF-kB, Bay11-7082, was used to treat ESCC cell lines co-cultured with M2 macrophages, followed by cell proliferation, migration, invasion assays and vascular endothelial growth factor (VEGF) secretion by ELISA. The effect of Bay11-7082 (5 mg/kg) against growth of ESCC tumor was tested in xenografted tumors. Results: PMA plus Th2 cytokines treatment promoted differentiation of U937 cells into M2 macrophages. When treated with Bay11-7082, proliferation, migration, invasion and induction of VEGF expression was significantly inhibited in M2 macrophage co-cultured ESCC cells with a down-regulation of IkBα expression. Tumor growth was significantly increased in M2 macrophage co-cultured ESCC cells compared to that of the non-co-cultured controls, which was significantly retarded by treatment with Bay11-7082. Conclusions: NF-kB pathway was activated in ESCC cell lines co-cultured with M2 macrophages with an increase in cell proliferation, cell motility and angiogenic factor in vitro and tumor growth in vivo, which were significantly suppressed by a NF-kB inhibitor, Bay11-7082. These results suggest a role of M2 macrophage in promoting aggressiveness of ESCC cells, possibly through an activation of NF-kB pathway that may serve as a potential therapeutic target for ESCC.
Metastatic colorectal cancer (mCRC) treatment: A high-volume, single-center, real-life experience.
Authors: Francesca Bergamo, Sara Lonardi, Francesca Battaglin, Valentina Angela Marsico, Isabella Paladina, Gino Crivellari, Antonella Galiano, Laura Rumano', Luisa Bellu, Elena Carcea, Gladis Bortoletto, Pasquale Fiduccia, Roberta Bertorelle, Enzo Mammano, Massimo Rugge, Umberto Cillo, Donato Nitti, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2016)

733 Background: Few data are available on outcome of clinical practice unselected patients (pts) with mCRC. Methods: We retrospectively collected data of pts with mCRC followed at our Institution from January 2010 to December 2013 evaluating the clinical characteristics, treatments and survival outcomes. Results: A total of 584 pts were evaluated, 461 were followed at our Center while 123 were seen for a second opinion. Median age was 66 ys (25-94), 59% were male, 63% had an ECOG PS = 0 while 11% ≥2. 33% had right colon primary, 68% synchronous metastatic (mts) disease and 70% a single mts site. 81% underwent surgery on primary and 41% on metastases. 51% were RAS mutated (mut) and 5% BRAF mut. 57 pts didn't receive any systemic treatment, 33 due to frail clinical conditions and 24 due to radical surgical approach (R0). Among 404 treated pts, 239 received all 3 available cytotoxic agents (oxaliplatin, irinotecan, 5FU), 324 bevacizumab and 98 anti-EGFR; 153 (38%) were enrolled in clinical trials. Median overall survival (OS) was 27.6 months (mo) for the entire mCRC population, 3.7 mo for untreated frail pts, 28.7 mo for treated pts while it is still not reached for untreated R0 pts. OS was significantly longer for pts receiving first line combination therapy (29 vs 17 mo, p &lt; 0.01) while a poor prognosis was confirmed for BRAF mut pts (p &lt; 0.001). In a multivariate analysis age &lt; 70, PS 0 and R0 surgery on mts disease showed a positive prognostic impact on OS while a right site of primary was a negative predictor of outcome. At logistic regression older age, low PS and peritoneal disease negatively affected the possibility to receive all 3 active drugs. Conclusions: Despite being an unselected population our outcomes are comparable with results of clinical trials in the corresponding period. We feel that such positive evidence derives from a personalization of treatment and a multidisciplinary approach to mts disease.