tbuckley/cabot-search huggingface dataset:
Quality of life in patients with advanced gastroesophageal (GE) adenocarcinoma treated with modified docetaxel, cisplatin, and fluorouracil (mDCF).
Authors: E. C. Smyth, Y. Y. Janjigian, E. Robinson, E. C. Sheehy, I. Karpenko, M. Capanu, D. P. Kelsen, M. A. Shah
Journal: Journal of Clinical Oncology (2011)

92 Background: Although DCF is a standard first line chemotherapy option for advanced GE adenocarcinoma, the regimen is associated with significant toxicity. Even so, time to detriment in quality of life (QoL) was significantly better with parent DCF than CF (Ajani, JCO 2007). Modified DCF (mDCF) has demonstrated less toxicity than parent DCF without compromising efficacy in two phase II studies (Shah, GI ASCO 2010; Kelsen, ASCO 2009). We report the quality of life (QoL) over time of patients receiving mDCF on these two clinical trials. Methods: Patients (pts) treated on two protocols utilizing the mDCF regimen, either alone or in combination with bevacizumab, were administered standard EORTC QoL questionnaires (QLC –C30 version 3), at baseline, 6 weeks, 3, 6, 9 and 12 months (m). Chemotherapy and QoL assessment continued until disease progression. Mean score change from baseline was assessed using Wilcoxon test. Results: 94 eligible pts have been enrolled on both studies; QoL questionnaires are available on 87 pts. 74% are male, median age 58 years (range 28-78), with baseline Karnofsky performance status of 80% (range 70-100). Patient compliance with QoL assessment was high at baseline but diminished with time; 89% of pts completed the questionnaire at baseline and 41% at 12m. There was no significant detriment in EORTC QOL scores (including global health, physical and social functioning and fatigue) during treatment with mDCF (Table). Conclusions: In patients with advanced GE cancer, we observed no detriment in QoL scores in patients receiving mDCF therapy. Specifically, physical and social functioning, fatigue, appetite, and global heath QoL scores were maintained at baseline levels during the first 6 months of therapy, and appear to improve in patients who remained on protocol therapy during the next 6 months of treatment. [Table: see text] No significant financial relationships to disclose.
Sorafenib versus sunitinib as first-line treatment in metastatic renal cell carcinoma: Largest multicenter retrospective analysis.
Authors: Xinan Sheng, Hailiang Zhang, Xuesong Li, Zhihong Chi, Zhisong He, Dingwei Ye, Jun Guo
Journal: Journal of Clinical Oncology (2016)

594 Background: For the mRCC patients, selecting the first-line regimen for a particular patient has become a hard decision for clinicians. However, there was few clinical studies directly comparing the efficacy of first-line treatment with sorafenib and sunitinib. Methods: Reviewing medical records at the Peking University Cancer Hospital, Fudan University Cancer Hospital and Peking University First Hopital from May 2005 to March 2015 revealed 483 patients receiving sorafenib (400 mg orally BID continuously in a 4-week cycle) and 362 patients receiving sunitinib (50 mg orally daily in a 6-week cycle; 4/2 schedule) as the first-line targeted therapy. Results: Median follow-up was 23.0 months (95% CI: 2.5-25.4 months).There was significant differences in progression-free survival (PFS) between the sorafenib and sunitinib groups (11.1 months [95% CI: 8.00-13.00] vs 10.0 months [95% CI: 9.00-14.00], respectively; P = 0.028) .No significant differences was seen in overall survival (24.0 months [95% CI: 20.00-29.00] vs 24.0 months [95% CI: 18.00-31.00], respectively; P = 0.298). A subgroup analysis based on Karnofsky performance status (KPS), pathological type, Memorial Sloan Kettering Cancer Center score, metastases, and tumor load was also conducted. Clinical benefit rate was higher in sorafenib-treated patients (94.67%) than sunitinib-treated patients (84.33%). Multivariate analysis revealed that sorafenib had superior efficacy in patients with a KPS of &lt; 90 and significantly better PFS (hazard ratio: 0.460 [95% CI: 0.222-0.954]). Conclusions: To our knowledge, this is largest mutli-center retrospective study determined the efficacy of sorafenib versus sunitinib as first-line therapy for mRCC patients. Our study results support administration of sorafenib as an effective first-line treatment agent in Chinese patients with mRCC.
Comprehensive Profiling of Somatic Mutations Which Define Primary Disease and Relapse in Various Acute Leukemia Subtypes
Authors: Vikas Madan, Wen-Wen Chien, Ding Ling Wen, Manoj Garg, Norimichi Hattori, Sun Qiaoyang, Henry Yang, Yasunobu Nagata, Kenichi Yoshida, Masashi Sanada, Yusuke Okuno, Tamara Alpermann, Ezhilarasi Chendamarai, Saravanan Ganesan, Daniel Nowak, Tsuyoshi Nakamaki, Norihiko Kawamata, Takayuki Ikezoe, Shirley, Kow Yin Kham, Jairo Matthews, Liu Lizhen, Meng Xuan, Lim Su Lin, Olga Blau, Steven M. Kornblau, Michael Andreeff, Shigeru Tomoyasu, Wolf-Karsten Hofmann, Allen Yeoh, Seishi Ogawa, Vikram Mathews, Torsten Haferlach, Lee-Yung Shih, Phillip Koeffler
Journal: Blood (2012)
Mice on trial: Are xenografts using human tissue a better model of cancer than xenografts formed from cell lines?
Authors: Gaitri Sadadcharam, Morgan McCourt, Ciara Ryan, Kate O'Connor, Michael William Bennett, Derek Gerard Power, Seamus O'Reilly, Jinghuai Wang, Henry Paul Redmond, Emmet J Andrews
Journal: Journal of Clinical Oncology (2013)

386 Background: Xenograft tumours are validated models using either patient samples (primary xenografts) or cell lines (secondary xenografts) grown in a murine host. Repeated culturing of cancer cell lines results in epigenetic changes and subsequent behaviour changes distinct from primary human cancers. The aim of this study is to form both models and compare their responses to chemotherapy agents. Methods: Fresh primary colorectal adenocarcinoma tissue or colorectal cell lines (SW480 non metastatic line / SW620 metastatic line) were inoculated subcutaneously into immunodeficient mice to form primary and secondary xenografts respectively. Both models were subjected to either a 5-fluorouracil (5-FU) or irinotecan trial. The clinical response and biological features were evaluated. Results: Secondary xenografts were more aggressive with a shorter time to tumour formation, higher uptake rate and more aggressive histological features. The mice were randomised to either the control group (saline) or to the treatment group [60mg/kg of 5FU (SW620 / primary xenografts) or 60 mg/kg of Irinotecan (SW480 / primary xenografts)] via intraperitoneal injection. In the 5FU group, the primary xenografts began regressing after Day 2 but the secondary xenografts continued to grow until Day 8. The decrease from the maximal tumor volume to the study end point (Day 12 in primary xenograft group and Day 10 in secondary xenograft group) was evaluated with primary xenografts showing a greater decrease compared to secondary xenografts (56.6% vs. 10.4%; p =0.002). Conclusions: We demonstrated the ability to grow tumours in mice from fresh human colonic adenocarcinomas. Tumours formed in mice from patient derived adenocarcinomas produce more clinically accurate testing than tumours formed from cell line and may allow for drug screening in order to personalise an individual’s chemotherapy regime.
Bortezomib (B) and doxorubicin (dox) in patients (pts) with hepatocellular cancer (HCC): A phase II trial of the Eastern Cooperative Oncology Group (ECOG 6202) with laboratory correlates
Authors: J. D. Berlin, M. E. Powell, Y. Su, L. Horton, S. Short, A. Richmond, J. S. Kauh, C. A. Staley, M. Mulcahy, A. B. Benson
Journal: Journal of Clinical Oncology (2008)

4592 Background: Until ASCO 2007, the there was no proven systemic therapy for HCC, but dox was used often because of a response rate (RR) of up to 10%. We tested the effects of B, dox and B + dox in HCC cell lines and mouse models and found dox + B to be at least additive compared to dox alone. Methods: Eligible pts had biopsy proven HCC with no prior chemotherapy or hormonal therapy, ECOG PS 0–2, with measurable and biopsiable disease. Pts had adequate bone marrow function (lower levels allowed for splenomegaly), bilirubin ≤ 2.0 mg/dl, Child’s Pugh class A or B cirrhosis, INR ≤ 1.5, no peripheral neuropathy of grade 2 or higher and normal ejection fraction. Primary endpoint is RR. Null hypothesis = 10% RR. 40 pts were planned (37 eligible) to give 91% power to detect RR of 27% (7 responses) with 1-sided significance of 0.07. Secondary endpoints were toxicity, survival (OS) and progression-free survival (PFS). Dox (20 mg/m2 initially, then changed to 15mg/m2 due to heme toxicity) was given days 1, 8 (day 1 dox was omitted in cycle 1) and B (1.3mg/m2) (from NCI/CTEP) was given days 1, 4, 8 and 11 of a 21-day cycle. Serum was analyzed prior to treatment, cycle 1 day 8 and cycle 2 day 8 for changes in chemokines/cytokines (CKS). Results: 42 pts accrued, 39 confirmed eligible: 28 male, 11 female; 27 white, 9 African American, 3 other; PS = 0 :6, PS = 1: 28, PS =2: 5. 1 response (2.3%, 90% CI [0.1%, 11.6%]) was seen. 10 (25.6%) pts had stable disease, 17 pts (43.6%) had progression. The null response rate of 10% was not rejected (one-sided p-value = 0.98). Median OS was 5.7 months (90% CI [4.4, 7.9]) and PFS was 2.4 months (90% CI [2.1, 3.0]). 28/39 had grade (gr) 3 toxicity, 11 had gr 4. Most common toxicities were gr 3 leukocytes (11 pts), gr 3 platelets (8 pts) and gr 4 platelets (8 pts). Gr 3 fatigue occurred in 7 pts and gr 3 diarrhea in 5 pts. CKS evaluations showed changes in serum levels of GROα, MIP-1α, IL-6 and IL-8 in several pts. Conclusions: Dox + B did not show significant activity in HCC. The regimen was generally well-tolerated with mostly hematologic toxicity and no toxic deaths. B caused changes in several CKS levels in pts with HCC. We will analyze the lab data to correlate with clinical efficacy and toxicity prior to the ASCO 2008 meeting. No significant financial relationships to disclose.
A phase I/II trial of melphalan (MEL) combined with panobinostat (PAN) for patients with relapsed or refractory (R/R) multiple myeloma (MM).
Authors: Ori Yellin, James R. Berenson, Ralph V. Boccia, Allen Lee Cohn, Paul Berard, Hassan Ghazal, Saad Jamshed, Edwin Kingsley, Wael A. Harb, Stephen J. Noga, Youram Nassir, Regina A. Swift, Robert A. Vescio
Journal: Journal of Clinical Oncology (2012)

e18558 Background: PAN, a potent histone deacetylase inhibitor, significantly inhibits the growth of MM cells in vitro and enhances the cytotoxicity of standard chemotherapy. Studies with our SCID-hu MM models show an increased inhibition of MM cell growth when PAN was combined with MEL compared to treatment with either drug alone. These preclinical studies provided the rationale for evaluating the combination of oral MEL with oral PAN for the treatment of MM patients with R/R disease. Methods: This was a Phase 1/2, open-label, dose‑escalation study to treat R/R MM patients initially using oral PAN every Monday, Wednesday and Fridayin combination with oral MEL (0.05 mg/kg) on days 1-5 of a 28‑day cycle. Results: Thirty-seven patients were enrolled into the Phase 1 portion of this study. The median number of prior regimens received were 4 (range, 1-17) with 22 patients previously treated with MEL. Following amendments to dose and schedule because of toxicity including cytopenias and fatigue, PAN and MEL were both administered only on days 1, 3 and 5 of a 28-day cycle. The maximum tolerated dose for this combination was defined as PAN at 20 mg and MEL at 0.05 mg/kg both administered on only days 1, 3 and 5. Overall, 4 patients (11%) showed objective responses to this combination with 1 complete (3%) and 3 partial (8%) responses and only occurred among patients receiving PAN throughout the cycle. An additional 18 (49%) patients had stable disease while 15 (41%) progressed while on study. Eighteen patients experienced grade 3 or 4 adverse events (AEs) with 6 of these meeting the definition of a dose-limiting toxicity. These AEs included reversible thrombocytopenia (n=11), reversible neutropenia (n=10), reversible worsening anemia (n=3), and one case each of a forearm rash, fatigue/weakness, pneumonia, hypokalemia and hyponatremia. Three more patients who are not yet evaluable have been enrolled into the Phase 2 portion to complete the planned 40 patients on the trial. Conclusions: The combination of intermittent PAN &amp; low-dose oral MEL shows modest activity in heavily pretreated patients with R/R MM. Continuous doses of PAN with MEL yielded better efficacy but this treatment schedule was not tolerable.
Discordance in estrogen receptor status between primary, metastatic, and second primary breast cancers: Impact of misclassification.
Authors: D. Huo, J. Liu, O. I. Olopade
Journal: Journal of Clinical Oncology (2011)

578 Background: The assessment of estrogen receptors (ER) is important for deciding hormone therapy for breast cancer (BC) patients. It is debatable as to whether ER status changes from primary tumors to metastatic lesions. It is also not clear on the degree of similarity between two primary BC. The discordance of ER status may represent genuine change in the biology of the disease. It may also be due to tumor heterogeneity and limited accuracy and reproducibility of receptor assays. Methods: We used a Bayesian method to assess the impact of misclassification on discordance in ER status. We embedded our beliefs about sensitivity (SN) and specificity (SP) in their priors. That is, the prior distribution is selected such that the 95% central interval (CI) for SN and SP of ER testing is (0.85, 0.95) or (0.80, 0.90). Data on ER status of two primary BC were from the Surveillance, Epidemiology, and End Results program. Data on ER status of primary/metastatic disease pairs were from meta-analysis of 13 studies after a literature review. Results: The observed discordance in ER status ranged from 15.3% to 19.4% between two pairs of BC, which essentially assumed that the ER testing assays had perfect accuracy (Table). If the SN/SP was between 0.85 and 0.95, the % discordance due to biological change would range from 9.6% to 12.7%. Conclusions: Our results suggest that a significant proportion of observed discordance in ER status is due to limited assay accuracy. Biopsy of metastatic sites for ER testing may be recommended on a case-by-case basis after considering the difficulty, cost, and side effects associated with tissue biopsy, as well as previous endocrine therapy. Our results also suggest that, for the majority of breast cancers (∼90%), ER expression is predetermined at the early step of carcinogenesis and the contribution of genetic drift or epigenetic regulation at metastatic sites is minimal. Percent discordance (no. of discordance/no. of patients) in ER status. Type of breast cancer pairs Perfect SN/SP 95% CI of SN/SP: 0.85-0.95 95% CI of SN/SP: 0.80-0.90 Two primary ipsilateral 15.3% (527/3,434) 9.6% 7.2% Two primary bilateral 19.4% (3,063/15,804) 12.7% 9.2% Primary and metastatic 17.3% (240/1,385) 11.6% 9.4%
Multivariable analysis of predictors of side effects of cabazitaxel in the Italian Expanded Access Program.
Authors: Giuseppe di Lorenzo, Carlo Buonerba, Sergio Bracarda, Donatello Gasparro, Angela Gernone, Caterina Messina, Vittorina Zagonel, Livio Puglia, Davide Bosso, Sabino De Placido
Journal: Journal of Clinical Oncology (2015)

225 Background: Cabazitaxel-based chemotherapy provides a survival benefit after docetaxel failure in patients with prostate cancer. Grade 3-4 neutropenia and febrile neutropenia were relatively frequent in the registrative trial, but their incidence in clinical practice is likely to be lower, as shown by data collected in the Expanded Access Program (EAP). While cumulative doses of docetaxel are associated to neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this study, we assessed 'per cycle' incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel. Methods: The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant side effects identified was assessed using a Generalised Estimating Equations (GEE) model at univariate and multivariate analysis. Multivariate logistic regression analysis was performed using a backward selection procedure. Variables with a p value ⩽0.1 were kept in the final model. Results: Per cycle incidence of grade 3-4 neutropenia was 8.7%, while febrile neutropenia occurred only in 0.9% of cycles and was an early event, occurring during the first three cycles only. Multivariate logistic regression analysis showed that the odds of having grade 3 – 4 neutropenia, febrile neutropenia and anemia were statistically significantly reduced by 10, 48 and 7%, respectively, every 10 mg/m2 increase of total prior dose of cabazitaxel. Interestingly, a body surface area &gt; 2 m2 was associated to increased odds of having grade 3-4 neutropenia. In this regard, it must be noted that all patients with body surface area &gt; 2 m2 had their total dose capped to 50 mg, with a mean (95% CI) and median (IQR) dose reduction of 7.1 (7.58-6.69) and 5.9 (2.76-10.27) % with respect to planned dose. Conclusions: Cumulative doses of cabazitaxel are associated to decreased risk of bone marrow toxicity. Patients with body surface area &gt;2 m2 are at increased risk of bone marrow toxicity and dose capping should be considered. These data indicate that cabazitaxel should not be arbitrarily suspended because of concerns of cumulative toxicity.
Survival and Prognosis in World Health Organization Defined Chronic Myelomonocytic Leukemia- A Mayo Clinic Series of 227 Patients
Authors: Mrinal M. Patnaik, Curtis A Hanson, Janice M Hodnefield, Ryan A Knudson, Rhett P Ketterling, Animesh Pardanani, Ayalew Tefferi
Journal: Blood (2012)
転移性大腸癌患者における第一選択療法として,セツキシマブ+カペシタビンおよびイリノテカン併用とセツキシマブ+カペシタビンおよびオキサリプラチン併用の比較: AIO KRK-0104 ドイツAIO CRC研究グループ無作為化試験
Authors: Moosmann Nicolas, Von Weikersthal Ludwig Fischer, Vehling-Kaiser Ursula, Stauch Martina, G Hass Holger, Dietzfelbinger Herrmann, Oruzio Daniel, Klein Stefan, Zellmann Klaus, Decker Thomas, Schulze Mathias, Abenhardt Wolfgang, Puchtler Gerhard, Kappauf Herbert, Mittermueller Johann, Haberl Christopher, Schalhorn Andreas, Jung Andreas, Stintzing Sebastian, Heinemann Volker
Journal: Journal of Clinical Oncology (2011)
Is adjuvant radiation plus chemotherapy for resectable pancreatic adenocarcinoma associated with improved survival? The Cleveland Clinic experience
Authors: R. E. Tsao, K. Almhanna, A. Lazaryan, P. Elson, R. Pelley, R. D. Kim, M. Walsh, M. Henderson, D. Vogt
Journal: Journal of Clinical Oncology (2008)

15528 Background: A large single-institution series of pts who recently underwent pancreaticoduodenectomy for resectable pancreatic cancer was analyzed to determine prognostic factors for overall survival (OS), including the impact of adjuvant radiation (XRT) and chemo (CT). Methods: Medical records were reviewed for 179 consecutive pts tx'd at The Cleveland Clinic w/ pancreaticoduodenectomy for resectable pancreatic adenoca. from 10/1999 to 12/2006. Clinical data was collected, Kaplan Meier method was used to estimate OS, and univariate/multivariate analysis was performed. Results: 179 pts with T1–3N0–1M0 pancreatic cancer met the above criteria. Median age at surgery was 67 (range 35–93) and median length of post-op hospital stay was 10 days. Peri-op mortality rate was 0.6%. 77% pts were R0 and 31% N0. Median OS for R0 pts = 20 mths [vs 16.3 mths for R1 (p=.86)]. Median OS for pts tx'd w/ XRT + CT was 28.1 mths [vs. 10.9 mths for pts receiving no adj. tx (p=.001)] (see table). In pts who relapse, the liver is the most common site (>50%). On univariate analysis, poor prognostic factors for OS were: poorly diff. histology (p=.002), >1 positive lymph node (p=.02), elevated AlkPhos (p=.01), elevated total bilirubin (p=.02), elevated AST (p=.05), age at dx >70 (p=.05), and high T-stage (p=.06). On multivariate analysis, poorly diff. histology, age >70, and elevated LFT's (AlkPhos or bilirubin or AST) were independent predictors of OS. Conclusions: In the 21st century, curative-intent surgery for pancreatic cancer at large academic institutions can have very low mortality rates. Pts who receive adj. XRT + CT appear to live longer than pts who receive no adjuvant therapy in this retrospective analysis. Pathology findings are valuable prognostic markers in resected pancreatic cancer. Few studies have examined the prognostic value of pre-op LFT's; our analysis indicates they may have predictive value - this should be confirmed in other series. Adj. Tx % pts Median OS (mths) XRT/CT + CT 22 23.3 XRT/CT 40 28.1 CT only 12 >28 No adj. tx 26 10.9 All pts - 19.6 No significant financial relationships to disclose.
Patients (pts) accessible to interview in palliative care unit: Analysis of inherent biases.
Authors: E. Fournier, C. Fournier, V. Christophe, M. Reich, S. Villet, V. Gamblin, D. Hoguet, I. Rodrigues, J. Neu, S. Clisant, N. Penel
Journal: Journal of Clinical Oncology (2011)

e19734 Background: Physical or psychological well-being is an essential component of quality care in palliative unit. The assessment of the psychological well-being is mainly based on interview and questionnaires. The aim of this study is to compare the clinical characteristics of cancer pts accessible to interview and those non accessible to interview. Methods: The clinical characteristics of 188 cancer pts admitted in palliative care unit from December 2006 to February 2008 have been collected. Characteristics of interviewable (80) and non-interviewable pts (108) have been compared. Dependence had been evaluated by nurses using the functional independence measure (Granger CV, et al. Top Geriatr Rehabil 1986;1:59-74). Results: Median age (62 vs. 63) and sex ratio (1.0 vs. 1.1) are similar in both groups. Lung primaries are significantly less frequent in interviewable pts (4% vs. 8%, p=0.005). Repartition of metastastic sites is similar in both groups. Body mass indexes are similar in both arms. Interviewable pts had had better performance status (IK≤30%: 49% vs. 21%, p<0.001). Interviewable pts had had better scores evaluating the functional dependence: capacity to feed (95% vs. 66%, p<0.0001), capacity to wash itself (81% vs. 55%, p<0.0001), capacity to get dressed (80% vs. 58%, p=0.02), urinary sphincter control (84% vs. 62%, p=0.002), digestive sphincter control mobility (86% vs. 67%, p=0.003) and the capacity to walk (79% vs. 52%, p<0.0001). Interviewable pts had better score for social interaction (100% vs. 79%, p<0.0001) or memory (100% vs. 76%, p<0.0001). The median overall survivals were respectively 6.6 weeks versus 2.6 (p=0.0004). Conclusions: Interviewable pts in palliative unit represent about 40% of all admitted pts. These pts are not representative of all pts since they had better performance status, they are less dependent and they experience significant better survival.
The interaction between bronchoconstriction and cough in asthma
Authors: Imran Satia, Huda Badri, Mark Woodhead, Paul M O'Byrne, Stephen J Fowler, Jaclyn A Smith
Journal: Thorax (2017)

Variable airflow obstruction is a pathophysiological hallmark of asthma; however, the interactions between acute bronchoconstriction and the cough reflex are poorly understood. We performed a randomised, single-blind, placebo-controlled, crossover study to investigate the interaction between bronchoconstriction and cough in asthma. Capsaicin was administered to evoke coughs and methacholine to induce bronchoconstriction. We demonstrated that acute bronchoconstriction increased capsaicin-evoked coughs, which improved as airway calibre spontaneously resolved. However, capsaicin-evoked coughing had no impact on methacholine-induced bronchoconstriction. This study provides evidence that bronchoconstriction increases the activation of capsaicin-responsive airway nerves, but the precise mechanisms and mediators involved require further evaluation. <h3>Trial registration number</h3> ISRCTN14900082.