tbuckley/cabot-search huggingface dataset:
Pain related to repeated invasive procedures in oncology: Improvement of management between 1998 and 2004
Authors: I. Krakowski, M. Di Palma, B. George, D. Serin, D. Feminier, P. Dielenseger, N. Vuillemin
Journal: Journal of Clinical Oncology (2005)

8247 Background: Two SOFRES surveys (1998 and 2004) on pain related to repeated invasive procedures were conducted among doctors, nurses and cancer patients. Objective: To measure the change in practices over 5 years, to analyse differences of pain assessment evaluated by healthcare professionals (doctors and nurses) and by patients, and to define better methods of management. Methods: Comparaison between 1998 and 2004:58/ 56 establishments,58/ 51 oncologist questionnaires, 113/105 nurse questionnaires, and 584/536 patient questionnaires were analysed Results: Patients: 35% versus (vs) 43% of males, 61% vs 54% of females, with a mean age of 54 vs 60 years, receiving adjuvant chemotherapy (25%vs 33%), metastatic first-line (36%vs 33%), metastatic post-first-line (34%vs 33%) for 1998 and 2004, respectively. 22.6 vs 24.6 procedures were performed for treatments (89% vs 87%). The most frequent painful procedures in 2004 were blood tests (86%), injections for radiological examinations (61%), and aspirations or biopsies (31%). Pain was not among the patient’s major complaints (9th position out of 12) during chemotherapy in 2004 and doctors and nurses classified pain in 8th position. On the other hand, pain was classified in 4th position out of 9 during repeated procedures. Pain caused by the various procedures appears to be overestimated by healthcare professionals. For patients and healthcare professionals, pain depends on who performs the injection especially after several metastatic lines (technical and relational skills). Pain related to invasive procedures affects the patient’s mental state, especially in the case of prolonged treatment. The number of central venous lines, relationships with the pain and palliative care teams and doctor-nurse communication and the use of local anesthetic techniques (15% vs 46%) increased between 1998 and 2004. Conclusions: Although management has improved since 1998, as patients demand analgesia less frequently, doctors manage pain directly without delegating to the nursing team, with more frequent use of anesthesia or systemic treatments, patients would like to be able to talk more freely about this pain and 25% of them would like an improvement of pain management. No significant financial relationships to disclose.
Predictive value of n-terminal telopeptide of type I collagen in patients with malignant osteolytic bone disease on bisphosphonates.
Authors: M. Joerger, A. Templeton, D. Koeberle, H. Engler, W. F. Riesen, B. J. Thurlimann
Journal: Journal of Clinical Oncology (2010)

e13047 Background: There is an urgent need for individualized treatment of patients with malignant bone disease (MBD), as the clinical benefit from bone-targeted therapies is moderate so far. As there is indirect evidence for N-terminal telopeptide of type I collagen (P1NP) to be involved in bisphosphonate resistance, we assessed the predictive value of P1NP for clinical outcome in patients with MBD receiving bisphosphonates. Methods: 70 patients with MBD were randomized to receive iv. pamidronate 60mg (n=35) or 90mg (n=35) for six 3-weekly cycles in a randomized, double-blind study (approved by the ethics committee). All patients had WHO pain score ≥2, modified WHO analgesic score ≥2, serum creatinine <350μmol/l, written informed consent. Median follow-up time is 14.8 years. Total serum P1NP concentrations were measured every three weeks by ELISA (gift from Roche Diagnostics, Basel). Baseline (continuous and categorical) P1NP concentrations were compared with pain response [visual analog scale (VAS), composite pain score (PPA)] and clinical outcome (skeletal-related events (SRE): Pathologic bone fracture, spinal cord compression, surgery to bone or radiation to bone) using Student's t, Wilcoxon rank-sum and log-rank test, respectively. The study has a power of 80% to detect a 20% difference in pain intensity (α=0.05, SD=15 mm on the VAS). Results: Patients with ≥20% pain reduction on the VAS had lower baseline P1NP concentrations as compared to patients with <20% VAS-response (146 vs. 323μg/L, p<0.0001). A negative correlation was found between baseline P1NP concentrations and maximum VAS-response (r= -0.59, p<0.0001) or PPA-response (r= -0.30, p=0.02) High baseline P1NP concentrations (highest tertile vs. lower two tertiles) were associated with a shorter duration of pain response (p<0.0001) and a shorter time interval to first SRE (p<0.008). Sensitivity for low baseline P1NP to predict freedom-from-SRE in the first year after treatment was 75%, specificity 82%. Conclusions: Serum P1NP has considerable predictive value for clinical outcome in patients with MBD receiving bisphosphonates. P1NP should be validated in studies with newer bone-targeted agents. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Over-expressed cyclooxygenase-2 in the diseased liver associates with clinical course of HCV-related cirrhotic patients after currative surgery for hepatocellular carcinoma
Authors: S. Morinaga, A. Kasahara, Y. Yamamoto, Y. Noguchi, Y. Rino, T. Imada, M. Akaike, Y. Sugimasa, S. Takemiya, K. Tarao
Journal: Journal of Clinical Oncology (2005)

4184 Background: The probable role of Cyclooxygenase-2 (COX-2) in chronic liver disease and hepatocellular carcinoma (HCC) development has been accepted to be relevant. The aim of this study was to determine whether over expressed COX-2 in the background liver affects the clinical course of HCV-related cirrhotic patients after curative surgery for HCC. Methods: Twenty-nine Clinical stage 1 HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in this study (22 men and 7 women, range 53–73 years old, follow up period; range 22 -159 months median 61). The patients were assigned to either low ALT group; the patients whose ALT levels monitored during the follow up period sustained lower than 80 IU, or high ALT group; the patients whose ALT level showed several peaks or plateaus equal to or over 80 IU. COX-2 expression was examined by immunohistochemistry using the avidin-biotin-peroxidase-complex technique on paraffin-embedded formalin-fixed tissue. The intensity of staining was scored in each hepatocytes, inflammatory cells, vascular endothelial cells, and bile duct epithelial cells; 1 = faint; 2 = moderate; 3 = strong, and the sum of the scores were defined as COX-2 expression score. Results: The COX-2 expression score ranged from 4 to 12 (median 8). The COX-2 expression scores were significantly higher in high ALT group (n =18) than in low ALT group (n = 11) (Mann-Whitney, P = 0.010). Nine patients were assigned to low COX-2 group (score 4, 5) and 20 patients to high COX-2 group (score 6–12). All the primary recurrent sites were the residual livers. The DFS of high COX-2 group was significantly poorer than that of low COX-2 group (Wilcoxon, P = 0.002). At univariate analysis, higher COX-2 expression and persistently high serum ALT levels were the significant factors for poorer DFS. The Cox multivariate analysis indicated that higher COX-2 expression in liver was the most important independent prognosticator for DFS. Conclusions: Over-expressed COX-2 in the background liver may play an important role in prolonged acceleration of necro-inflammation and recurrence/new development of HCC in HCV-related cirrhotic patients. No significant financial relationships to disclose.
Patient-derived xenograft platform to guide precision medicine in bladder cancer.
Authors: Chong-Xian Pan, Hongyong Zhang, Tzu-yin Lin, Clifford Tepper, James Keck, Paramita Ghosh, Susan D. Airhart, Carol J. Bult, David R. Gandara, Christopher P. Evans, Edison T. Liu, Ralph deVere White
Journal: Journal of Clinical Oncology (2015)

315 Background: The prognosis for bladder cancer has not changed in 30 years. No targeted agents have been approved even though reproducible genetic abnormalities have been identified. The goal of this project was to develop and characterize a patient-derived xenograft (PDX) platform to determine the efficacy of molecularly guided targeted and chemotherapy therapy, drug re-purpose, study resistance mechanisms, and design novel therapy to overcome resistance. Methods: PDXs were developed from direct implantation of uncultured patient bladder cancer specimens into immunodeficient NSG mice. Deep sequencing in combination with computational biology was performed to characterize PDXs and identify druggable genetic aberrations that guided efficacy screening and mechanistic studies. Results: Nineteen PDXs have been established with annotated clinical information. PDXs retained morphology and 92-97% genetic aberrations of parental patient cancers. Deep sequencing revealed multiple druggable genetic aberrations, including the fibroblast growth factor receptor 3 (FGFR3) and other tyrosine kinase receptor pathways. Compared to the progression-free survival (PFS) of 9.5 days in the control arm, matched therapy with an FGFR3 inhibitor BGJ398 prolonged PFS to 18.5 days (p=2.61 X 10 -6 ) in PDXs overexpressing FGFR3. Serial biopsies during treatment revealed reactivation of the downstream pathways coincided with development of resistance while targeting these downstream effectors reversed resistance (12 vs. 22 days, p=0.001). Efficacy studies also revealed that PDXs had differential response to chemotherapeutic drugs that could potentially guide selection of chemotherapeutic drugs for first- and second-line therapies. To determine the clinical applicability of non-myoinvasive bladder cancer, we further developed an orthotopic PDX model that mimiced disease progression to invasive and metastatic bladder cancer. Conclusions: The PDX platform allows screening for multiple targeted therapy, chemotherapy or combinations simultaneously for the most efficacious drugs or combination, and serial biopsies during treatment to study drug resistance, a task not possibly replicable at the clinical setting.
Phase II study for determining usefulness of FDG-PET as imaging biomarker in regorafenib treatment for metastatic colorectal cancer (JACCRO CC-12).
Authors: Masato Nakamura, Hironaga Satake, Akihito Tsuji, Tamotsu Sagawa, Akinori Takagane, Takashi Sekikawa, Wataru Ichikawa, Kazuhiro Oguchi, Tomohito Kaji, Mitsugu Kochi, Masashi Fujii, Masahiro Takeuchi, Toshifusa Nakajima
Journal: Journal of Clinical Oncology (2016)

TPS772 Background: Regorafenib (rego) is a novel multikinase inhibitor. A clinical, placebo-controlled phase III study (CORRECT) showed a 1.4-month improvement in Overall Survival (OS) as compared to the placebo group (HR 0.77, p = 0.0052) for metastatic colorectal cancer (mCRC). In the CORRECT trial, the Progression Free Survival (PFS) curve showed that half of the patients in the rego group showed a similar tendency to the placebo group. The finding suggested that patients might be divided into responders and non-responders, and there might be a biomarker to predict them. Although various studies including the CORRECT trial have searched for the biomarker of rego, it still has not been established. On the other hand, tumor metabolic analysis using FDG-PET has been reported to be more sensitive than the change of tumor size using CT to predict the response of molecular targeting therapies. We conducted a prospective multicenter phase II trial to identify the usefulness of FDG-PET as an imaging biomarker for rego. Methods: The main eligibility criteria are as follows; pathologically proven mCRC, sufficient organ functions, failure of standard therapies (fluorouracil, oxaliplatin, irinotecan and any biologic agents), with tumors detected by FDG-PET. The treatment schedule consists of 160mg once-daily oral administration of rego for 3 weeks, followed by 1 week of rest. On day 28, FDG-PET is re-taken and the change of the maximum standardized uptake value (SUVmax) from that of the pre-treatment examination is evaluated. The primary endpoint is the change of SUVmax in the region with the highest value in pretreatment FDG-PET. Secondary endpoints are changes of SUVmax in top 5 regions (maximum 2 regions in one organ), OS, PFS, response rate, disease control rate, adverse events, and correlation of their clinical parameters and changes of SUVmax. Because there has been no data about early change in SUVmax when rego was used, we set the threshold value and estimate value as 0% and 10%, respectively. Assuming a one-sided alpha of 2.5% and a power of ≥ 90%, 16 subjects are required, and a target sample size of 20 patients was determined. Ten of the planned 20 patients have been enrolled. Clinical trial information: UMIN000015563.
Phase II study of S-1 in patients with advanced or recurrent cervical cancer
Authors: Y. Hirai, N. Katsumata, S. Kamiura, T. Sugiyama, K. Kokawa, M. Hatae, R. Nishimura, K. Ochiai
Journal: Journal of Clinical Oncology (2008)

5514 Background: S-1, an oral fluoropyrimidine combination drug, is active agent against many types of cancer. This phase II study was designed to evaluate the efficacy and safety of S-1 in uterine cervical cancer. This is the first clinical study of S-1 in gynecologic cancer. Methods: The subjects were women 20 to 74 years of age with stage IVB or recurrent cervical cancer who had measurable disease and had not received more than one platinum-containing regimen of chemotherapy since the diagnosis of IVB disease or recurrence. The primary endpoint was the overall response rate (ORR) according to RECIST. The study comprised two stages: 20 patients were scheduled to be enrolled in the first stage, and 15 in the second (total 35). S-1 was given twice daily for 28 days, followed by 14 days of rest. Results: A total of 37 patients were enrolled between October 2005 and April 2007. One patient was ineligible. Of the 36 eligible patients, 34 had recurrent disease, 31 had received prior radiation therapy, and 21 had received prior chemotherapy. A median of four cycles of chemotherapy was given (range: one to 17+ cycles). The ORR was 33.3% (12/36, 95% CI: 18.6% - 51.0%). The most frequent grade 3/4 toxicities were anemia (16.2%), neutropenia (8.1%), diarrhea (21.6%), and anorexia (16.2%). There were no treatment-related deaths. Conclusions: S-1 monotherapy seems highly active and well tolerated in women with advanced or recurrent carcinoma of the uterine cervix. Further studies of S-1 in women with gynecologic cancer are warranted. No significant financial relationships to disclose.
Association of the establishment of multidisciplinary (MDC) hepatocellular carcinoma (HCC) clinic with clinical outcome.
Authors: Adam C. Yopp, Katherine T Ostapoff, Amit G Singal, John C. Mansour, Glen C. Balch, Jorge A. Marrero, Roderich Schwarz
Journal: Journal of Clinical Oncology (2013)

332 Background: Multidisciplinary clinics are prevalent in the management of cancer. However, there is a lack of data demonstrating improved outcomes. The variability of liver- and tumor-specific factors in HCC mandates multimodal therapy. The aim of this study was to evaluate the impact of establishing a MDC HCC clinic. Methods: A MDC HCC clinic consisting of surgeons, hepatologists, oncologists, and radiologists was established October 2010. After this date, any patient with HCC or suspected HCC (any liver mass on radiology or elevated AFP) was evaluated in the MDC clinic. We conducted a retrospective review of a prospective HCC database to identify patients diagnosed in the year following and three years prior to initiation of the MDC clinic. Demographics, tumor characteristics, treatment regimens, and survival were compared between the two groups of patients with one-way ANOVA and Chi-squared tests. Survival curves were generated using Kaplan-Meier with log rank test. Results: 105 patients were identified in the year prior to the MDC clinic and 209 patients in the 3 previous years. There was no difference in gender, race/ethnicity, etiology of cirrhosis, or Child-Pugh stage between the groups. Patients diagnosed after the MDC clinic were found at earlier tumor stages by AJCC and BCLC classification (p=0.001 and p=0.003, respectively). More post-clinic patients received treatment (56% vs. 44%, p=0.04), and time-to-treatment was shorter (2.2 vs. 4.6 months, p=0.001) than those diagnosed prior to the MDC clinic. Median survival of patients diagnosed after the MDC clinic was significantly longer than those seen during the 3 prior years (15.2 vs. 4.7 months, p=0.002). This difference in survival persisted when patients who were lost to follow-up or died within one month of HCC diagnosis were excluded (17.7 vs. 7.0 months, p=0.004). Survival after excluding BCLC D patients was also longer in the post-clinic period (one year survival, 64% vs. 47%, p=0.001). Conclusions: Formation of a MDC HCC clinic is associated with improved survival, most likely due to more streamlined care resulting in HCC diagnosis at earlier tumor stage and shorter time to treatment.
Exploring factors in diagnostic delays of head and neck cancer at a public hospital.
Authors: D. W. Lai, S. A. Buckley, B. L. Schmidt, C. Viet, F. Muggia, I. Belitskaya-Levy, R. F. Cohen, M. D. DeLacure, N. Sanfilippo, D. Myssiorek, D. Hirsch, N. Seetharamu
Journal: Journal of Clinical Oncology (2011)

5544 Background: Diagnosis and management of squamous cell carcinoma of the head and neck (SCCHN) involves a multidisciplinary approach. Navigation through a public hospital and the involved services often results in frequent diagnostic delays. Aims: 1. To quantify “provider delay:” the time between the first contact with health care provider and the time the diagnosis was confirmed by biopsy. 2. To determine what factors influence the delay in diagnosis. Methods: We extracted data from patients diagnosed with SCCHN in the years of 2007 to 2009. We then performed univariate analysis including Mann-Whitney, chi-square, and ANOVA tests to examine associations between provider delay and the following characteristics: language (English or Non-English), employment, presence of partner, gender, ethnicity, age (<45 or ≥45), cancer subsite, staging, number of co-morbidities (≤3 or >3 conditions), number of tobacco pack-years, and history of alcohol dependence. Results: We retrieved data on 117 SCCHN patients diagnosed in the years 2007 to 2009. The mean provider delay for all patients was 67.3 days, with a standard deviation (SD) of 116. We found a significant difference in two characteristics. Provider delay was significantly shorter (p= 0.05) for non-English speakers than English speakers. In addition, there was a trend of shorter provider delay (p= 0.06) when patients were unemployed compared to patients with employment. We found no significant associations between provider delay and the other variables listed above. Conclusions: These results counter the notion that the lack of English literacy and unemployment present disadvantages to the patient. We hypothesize that shorter provider delays are seen in non-English speakers because they have better social support. Our observation that provider delay is dissimilar in different subsets of patients suggests that this delay is amenable to interventions. Our future analyses will focus on the role of social support and interventions to reduce provider delay. No. of patients Mean (days) SD (days) Non-English speakers 30 25 31.9 English speakers 64 89.1 141 Unemployed 55 51.6 84.6 Employed 16 129 200
The effect of postoperative morbidity on long-term survival after curative resection for extra-hepatic biliary tumors: A multi-institution analysis from the U.S. Extrahepatic Biliary Malignancy Consortium.
Authors: Linda Jin, Bradley Krasnick, Jesse Davidson, Cecilia Grace Ethun, Timothy M. Pawlik, George A. Poultsides, Thuy Tran, Kamran Idrees, Chelsea A Isom, Sharon M. Weber, Ahmed I. Salem, Charles Raben Scoggins, Perry Shen, Harveshp Mogal, Carl Richard Schmidt, Eliza W Beal, Ioannis Hatzaras, Shishir Kumar Maithel, Ryan C. Fields
Journal: Journal of Clinical Oncology (2016)

435 Background: Surgical resection is the cornerstone of curative therapy for extrahepatic biliary tumors (EHBTs) Postoperative complications (POCs) can negatively impact survival after oncologic resection. We evaluated the impact of POCs on survival after resection of EHBTs. Methods: We analyzed 914 patients from ten institutions of the U.S. Extrahepatic Biliary Malignancy Consortium who underwent curative resection for gallbladder adenocarcinoma (n=389), hilar (n=295) and distal (n=294) cholangiocarcinoma between 1998 and 2015. POCs were graded using the modified Clavien-Dindo system. Overall survival (OS) probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. Results: Median follow-up was 20 months. The median age was 66 years, and the overall complication rate was 54%. Complication rates were significantly higher in patients with distal or hilar cholangiocarcinoma (62%) when compared with gallbladder cancer (41%, p&lt;0.001). For all cancer types, patients who experienced POCs had lower 5-year OS when compared with those who did not (18% vs 28%, p&lt;0.001). On multivariate Cox regression, POC remained an independent predictor for decreased OS (HR 1.5, 95% CI 1.3-1.9, p&lt;0.001; Table). Among patients who experienced POCs, survival did not differ by greatest Clavien grade of complication experienced (p=0.89), however patients who had 2 or more POCs did have decreased long term survival when compared with patients with only a single POC (HR 1.5, 95% CI 1.2-1.8, p=0.001). Conclusions: POCs adversely affect long-term outcomes after curative resection for extra-hepatic biliary tumors. While any complication grade did not have a significant impact on long-term survival, increasing number of POCs did significantly worsen the prognosis for OS. [Table: see text]
Nanoparticles Formed by Acoustic Destruction of Microbubbles and Their Utilization for Imaging and Effects on Therapy by High Intensity Focused Ultrasound
Authors: Nicholas T. Blum, Adem Yildirim, Rajarshi Chattaraj, Andrew P. Goodwin
Journal: Theranostics (2017)

This work reports that when PEG-lipid-shelled microbubbles with fluorocarbon interior (C4F10, C5F12, or C6F14) are subjected to ultrasound pulses, they produce metastable, fluid-filled nanoparticles that can be re-imaged upon administration of HIFU. The nanoparticles produced by destruction of the microbubbles (MBNPs) are of 150 nm average diameter and can be re-imaged for up to an hour after creation for C 4F10, and for at least one day for C5F12. The active species were found to be fluid (gas or liquid) filled nanoparticles rather than lipid debris. The acoustic droplet vaporization threshold of the nanoparticles was found to vary with the vapor pressure of the encapsulated fluorocarbon, and integrated image brightness was found to increase dramatically when the temperature was raised above the normal boiling point of the fluorocarbon. Finally, the vaporization threshold decreases in serum as compared to buffer, and administration of HIFU to the nanoparticles caused breast cancer cells to completely detach from their culture substrate. This work demonstrates a new functionality of microbubbles that could serve as a platform technology for ultrasound-based theranostics.