tbuckley/cabot-search huggingface dataset:
The use of opioids not recommended in guidelines in Taiwan cancer patients.
Authors: Han-Chung Emily Hsiue, Chih-Peng Lin, Wen-Ying Lin, Ho-Min Chen, Ann-Lii Cheng, Mei-Shu Lai, Yu Yun Shao
Journal: Journal of Clinical Oncology (2015)

e20721 Background: Opioids are crucial for cancer pain management, but not all opioids are recommended by guidelines. We examined the use of opioids not recommended by the National Comprehensive Cancer Network (NCCN) guideline in Taiwan cancer patients. Methods: We reviewed the claims database of National Health Insurance of Taiwan. All patients who had cancer diagnosis (ICD-9: 140-208) from 2003 to 2011, either at inpatient or outpatient services, were enrolled. The usage and cost of non-opioid and opioid analgesics were identified and calculated by calendar year. Opioids were classified to 3 categories (not recommended: propoxyphene, nalbuphine, and meperidine; strong opioids: morphine and fentanyl patches; weak opioids: tramadol, buprenorphine, and codeine) and investigated separately. We used WHO defined daily dose to calculate the use of different opioids. Results: A total of 1,424,048 cancer patients were enrolled; 53% were male and the median age was 60 years. The most common primary sites of malignancy were colon and rectum, liver, lung, breast, and prostate. The percentage of opioid users (~25%) among cancer patients was stationary in the study period, but the percentage of opioid users among analgesics users increased from 48.2% to 51.0%. Among opioid users, the percentage of patients who had ever used opioids not recommended by guidelines decreased from 66.7% in 2003 to 45.7% in 2011. Comparing the opioid use among the three categories, opioids not recommended contributed only 10% of opioid use. Strong and weak opioids contributed approximately 50% and 40% of the opioid dose, respectively. Among patients who had received opioids not recommended by guidelines, 83.4% to 97.7% of them had ever received meperidine. However, the use of meperidine per patient was low, and propoxyphene instead had the highest use. In the study period, the annual costs of opioids not recommended by guidelines were approximately 0.4 million US Dollars, which were only 2% to 4% of total opioid costs in Taiwan cancer patients. In 2011, propoxyphene was prohibited, and the use of opioids not recommended contributed only 2% of all opioid use. Conclusions: Among the study period, the use of opioids not recommended by NCCN was limited in Taiwan cancer patients.
局所進行性直腸癌の術前放射線化学療法後の腫瘍縮小グレード再考: CAO/ARO/AIO-94試験結果の最新情報
Authors: Fokas Emmanouil, Liersch Torsten, Fietkau Rainer, Hohenberger Werner, Beissbarth Tim, Hess Clemens, Becker Heinz, Ghadimi Michael, Mrak Karl, Merkel Susanne, Raab Hans-Rudolf, Sauer Rolf, Wittekind Christian, Roedel Claus
Journal: Journal of Clinical Oncology (2014)
Phase I trial of docetaxel (D), prednisone, and pasireotide (P) (SOM230) in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Hema M. Vankayala, Lance K. Heilbrun, Kimberlee Dobson, Karri Stark, Jing Li, Daryn W. Smith, Ulka N. Vaishampayan
Journal: Journal of Clinical Oncology (2014)

5060 Background: Neuroendocrine (N) differentiation is a resistance mechanism to chemotherapy in mCRPC. Somatostatin (sst) receptor analogs demonstrate efficacy in N tumors. P is a multitargeted sst -receptor analog with affinity to sst 1, 2, 3 and 5, and the potential to overcome chemoresistance. A phase I trial of D+P was conducted to establish the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D). Methods: Chemotherapy naïve mCRPC patients (pts) with performance status (PS) 0-2 and adequate renal and hepatic function were enrolled. D was administered at a dose of 75 mg/m2 intravenously every 21 days and P was administered intramuscularly (IM) every 28 days at escalating dose levels of 40, 60, and 80 mg. A 3 + 3 study design was utilized. Correlative studies included circulating tumor cell counts (CTC), IGF-1, neuron specific enolase (NSE), and chromogranin A (ChA) levels pre and post therapy. Results: Phase I portion of the study is complete. 12 pts were enrolled with a median age of 65 years (range 54-74) and PS of 1. Gleason score was > 8 in 8 pts. 4 pts had visceral metastases. Pre-study regimens included, enzalutamide (2pts); abiraterone (2 pts); and clinical trial agents (4 pts). Dose limiting toxicity noted at 80 mg of P were, grade 4 hyperglycemia unresponsive to therapy and 1 with grade 4 neutropenia lasting for > 7 days. The RP2D of P is 60 mg every 28 days in combination with D 75 mg/m2 every 21 days. 4 of 6 pts at 60 mg of P had grade 3 hyperglycemia. No cholelithiasis, severe liver toxicity, or treatment related deaths were noted. 8 pts had grade 1-2 diarrhea, and 1 had grade 3 diarrhea. A median of 6.5 (range 2-14) cycles of D and 5 cycles (1-13) of P were administered. To date, 9 pts have progressed with median time to progression of 8.3 months (range 1.4 - 10.4) which compares favorably with docetaxel therapy alone (median 6.3 months). 3 of 6 pts with pretreatment CTC > 5 converted to CTC < 5 post therapy. Of the markers, only IGF-1 levels revealed a median 51% decrease with therapy. Conclusions: The addition of P to D is clinically feasible at a dose of 60 mg IM every 28 days. Clinical efficacy is encouraging and warrants study in the phase II setting. Supported in part by Novartis Inc. Clinical trial information: NCT01468532.
Prognostic significance of multifocalty in papillary thyroid carcinoma: A multivariate analysis of prognostic factors.
Authors: Ivan Markovic, Radan Dzodic, Srdjan Nikolic, Igor Djurisic, Merima Oruci, Aleksandar Martinovic, Gordana Pupic, Zorka Milovanovic, Zorica Tomasevic
Journal: Journal of Clinical Oncology (2014)

6038 Background: The incidence of multifocality in papillary thyroid carcinoma (PTC) was refered form 18 to 87,5%. The mechanisms of multifocal spreading, corelation with tumor size and histology variants of PTC, presence of lymph node metastases, as well as prognostic significance of multifocality has not yet been clarified. Methods: One hundred fifty three patients with PTC were surgicaly treated. Patients with locally invasive tumors (pT4) and initial distant metastases were excluded from study. Median age 42 years at diagnosis. Sex ratio: F/M-3.9/1. Total thyroidectomy (TT) was done in all 153 patients. Dissection of central and lower jugular lymph nodes of the neck for frozen-section histology was done in 117 (76.5%) patients and modifed radical neck dissection if positive. Statistics: Kapplan-Meier, Log Rank, Cox`s multivariate regresion model. Results: Multifocal tumors were found in 43 (28%) thyroid gland specimens. The smallest focus was 2 mm. The incidence of multifocality was significantly higher in patients above 45 years at diagnosis (p<0.05) and in tumors greater than 4 cm in diameter (p<0.01). Multifocality was not significantely corelated with gender, histology variants of PTC or presens lymph node metastases (LNM). Incidence if LNM in patients with multifocal PTC was 29% vs. 44% in patients with solitary tumors. In a median follow up of 138 months (rang =2-229) regional relaps in not dissected lymph nodes occurred in 13 (8.4%) and distant metastases in 2 (1.3%) patients, while 8 (5.2%) patients died due to PTC. Incidence of relapse was significantly higher (p<0.01), and relapse free interval and survival significantly shorter (p=0.0095, p=0.0004, respectively) in patients with multifocal PTC. According to Cox`s multivariate regrresion model, multifocality was independent prognostic factor for both relapse and survival in patients with intrathyroid papillary carcinoma. Conclusions: Due to high incidence of multifocality, higher relapse rate and worse survival, total thyroidectomy should be consider as optimal treatment in patients with PTC, in a goal to reduce relapse rate and improve disease free and overall survival.
A Phase 1/2 Trial of Investigational Spk-8011 in Hemophilia a Demonstrates Durable Expression and Prevention of Bleeds
Authors: Katherine A. High, Lindsey A. George, M. Elaine Eyster, Spencer K. Sullivan, Margaret V. Ragni, Stacy E. Croteau, Ben J. Samelson-Jones, Matthew Evans, Marcelyne Joseney-Antoine, Amy Macdougall, Judith Kadosh, Alexa R. Runoski, Cynthia Campbell-Baird, Kayla Douglas, Summer Tompkins, Howard Hait, Linda B. Couto, Ashlyn Eaton Bassiri, Leonard A. Valentino, Marcus E. Carr, Daniel J Hui, Katie Wachtel, Daniel Takefman, Federico Mingozzi, Xavier M. Anguela, Kathleen B Reape
Journal: Blood (2018)
Multicenter phase II study of nedaplatin (NP) and irinotecan (CPT) for patients with advanced squamous cell cancer (SCC) of the Lung thoracic Oncology Research Group (TORG 0910).
Authors: Haruhiro Saito, Kouzo Yamada, Noriyuki Masuda, Yuichi Takiguchi, Yukio Hosomi, Hiroaki Okamoto, Kazuma Kishi, Fumihiro Oshita, Koshiro Watanabe
Journal: Journal of Clinical Oncology (2014)

e19057 Background: Three-dimensional analytical models demonstrated a synergistic interaction of NP and CPT (Clin Cancer Res 2001).The phase I/II studies showed high activity of NP and CPT in lung cancer (Cancer Chemother Pharmacol 2003) and meta-analysis suggested that a NP and CPT regimen was more feasible in SCC (J Thorac Oncol. 2011). Methods: We conducted a multicenter phase II study of NP and CPT for stage III and IV SCC of the lung. Chemotherapy treatments consisted of 4 to 6 cycles of NP at 100mg/m2 (day 1) and CPT at 60mg/m2(days 1 and 8) every 4 to 5 weeks. The primary endpoint was the response rate and the secondary endpoints were overall and progression-free survival rates and safety. Results: Fifty patients were registered and evaluated. Twenty-seven patients received 4 to 6 cycles of chemotherapy. The median number of cycles was four. Major toxicities were 10.0% of grade 4 anemia, 46.0% neutropenia and 10.0% thrombocytopenia, and there were 22.0%, 12.0%, 12.0%, 16.0% and 10.0% of grade 3 or 4 anorexia, diarrhea, hyponatremia, febrile neutropenia and infection, respectively. Each of the toxicities was controllable and there were no treatment-related deaths. One patient achieved a complete response and there were 16 partial responses, with an overall response rate of 34.0% (95% confidence interval 21.2% to 48.8%). The disease control rate was 74.0%. The median progression free survival time was 4.3 months. Conclusions: An NP and CPT regimen is feasible for patients with advanced SCC of the lung. Clinical trial information: 000003330.
A phase Ib/II study of cetuximab and pembrolizumab in RAS-wt mCRC.
Authors: Patrick McKay Boland, Alan Hutson, Orla Maguire, Hans Minderman, Christos Fountzilas, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2018)

834 Background: Cetuximab is a chimeric IgG1 anti-EGFR monoclonal antibody approved in RAS-wt metastatic colorectal cancer (mCRC). Pre-clinical data have suggested that cetuximab triggers immunogenic cell death and support an immunologic basis of activity. Small clinical data sets demonstrate that EGFR-based therapy preferentially increases TILs in colorectal hepatic metastases. This Phase Ib/II study was designed to assess the safety and clinical activity of cetuximab and pembrolizumab in metastatic colorectal cancer. Methods: Eligible pts were those with RAS-wt mCRC, ECOG performance status (PS) 0-2, with at least 1 prior line of therapy for advanced stage disease, and no prior treatment with an anti-EGFR antibody. The phase Ib study was designed as a safety lead-in with a de-escalation design. Pembrolizumab was administered at a fixed dose of 200 mg q3week with standard cetuximab dosing (400 mg/m2 loading dose, followed by 250 mg/m2 weekly). DLTs were defined as any ≥ grade 3 clinically significant toxicity which is possibly related and occurs within the first 6 weeks of therapy. For rash and hypomagnesemia only ≥ grade 4 toxicities were considered DLTs. Correlative serial biopsies were performed at baseline and at 9 weeks. Results: 9 patients, ages 33-73, were enrolled onto the Phase Ib study between 8/10/16 and 11/2/16. No DLTs were observed. The most common AEs of any cause observed were xerosis, dermatitis acneiform rash, hypomagnesemia, vomiting, and fatigue. ≥ Grade 3 toxicities were uncommon, but included hypomagnesemia (3), rash (1), urticaria (1), hypocalcemia (1), alk phos elevation (1), and ascites (1). 6/9 patients achieved stable disease lasting ≥ 16 weeks. Conclusions: The combination of cetuximab and pembrolizumab is well-tolerated in this study and can be administered at full dosages. Though hypomagnesemia appears prominent, no additional emergent AEs have been observed during or following the DLT period. The associated ongoing phase II study will enroll an additional 33 patients to assess the true efficacy of this regimen with dual primary endpoints of ORR and 6 month PFS. Clinical trial information: NCT02713373.
Arobase: A phase III trial of exemestane (Exe) and bevacizumab (BEV) as maintenance therapy in patients (pts) with metastatic breast cancer (MBC) treated in first line with paclitaxel (P) and BEV—A Gineco study.
Authors: Olivier Tredan, Philippe Follana, Isabelle Moullet, Claire Cropet, Stéphanie Trager-Maury, Jérôme Dauba, Sandrine Lavau-Denes, Veronique Dieras, Dominique Beal-Ardisson, Marie-Claude Gouttebel, Hubert Orfeuvre, Eric Pujade-Lauraine, Thomas Denis Bachelot
Journal: Journal of Clinical Oncology (2014)

501 Background: Combination of P+BEV significantly improves progression-free survival (PFS) in MBC pts, but is associated with adverse events (AEs), mainly neuropathy and fatigue worsening over time. Endocrine therapy (ET) combined to BEV has been proven tolerable and may be a option as maintenance therapy after P+BEV. Methods: in this prospective, randomized, open label, phase III study, pts with histologically confirmed ER+ HER2- locally advanced or MBC, who had not progressed after 16-24 weeks of 1st-line P+BEV therapy, were randomized to P+BEV continuation vs ET+BEV (Exe 25 mg/d+BEV 15 mg/kg q3w). Primary endpoint was PFS. To demonstrate an improvement in the 6-month PFS rate (PFS-6m) from 50% with P+BEV to 65% with ET+BEV (2-sided α=5%) with 80% power, 141 events were requiered and 198 pts were planned. An interim analysis (IA) was planned after 40% of required events. Secondary endpoints included overall survival (OS) and toxicity. Results: At the cut-off date for the IA (May 2013), 113 pts were included, 98 were analyzable. Median age was 55 (range 35-86). ET was given as adjuvant therapy in 64% of pts and in the metastatic setting in 24%. Median follow up was 9.7 months (range 0.8-28.3). PFS-6m was 70% (95% confidence interval (CI) 54, 81.5) with P+BEV and 54% (95% CI 38.5, 67.2) with ET+BEV (HR 1.2, 95% CI (0.7, 1.9), p=0.56). Given these interim results, the probability to show statistically significant PFS at the end of the study was 7%. Deaths were reported for 11 pts in the P+BEV arm vs 6 pts in the ET+BEV arm (median OS not reached). Grade 3-4 AEs rates were lower with ET+BEV (fatigue: 4% of pts vs 14%); neuropathy: 0% vs 12%; pain: 2% vs 8%; neutropenia: 0% vs 12%), as well as serious AEs related to treatment (13% vs 24%). Based on both safety and efficacy results, the IDMC decided to definitely stop the enrollment and to keep patients under tretment in the protocol.Follow-up data will be updated for the final analysis. Conclusions: The efficacy hypothesis was not reached, despite a better safety profile of the ET+BEV maintenance therapy. Exploratory analyses are planned to identify potential subgroups benefiting from it. Clinical trial information: NCT01303679.
The biological characteristics and kinetics of circulating tumor cells in hepatocellular carcinoma undergoing surgical interventions.
Authors: Yunfan Sun, Jia Fan, Xin-Rong Yang, Yang Xu
Journal: Journal of Clinical Oncology (2014)

e22013 Background: Little is known on the biological variability and kinetics of CTCs in the patients with localized cancer. Herein, we investigated biological characteristics of CTCs at different vascular sites and their dynamic changes after surgical interventions in HCC patients. Methods: CTCs from 30 HCC patients were quantified by CellSearch before and at intervals up to 1 month after open (n=13) or laparoscopic resection (n=7), open radiofrequency ablation (RFA) (n=5), or percutaneous RFA (n=5). For 12 of 18 patients treated with open surgery, CTCs were examined in peripheral vein (PV), peripheral artery (PA), suprahepatic inferior vena cava (SHIVC), infrahepatic inferior vena cava (IHIVC) and portal vein (PoV). Results: The median number of CTCs in PV, PA, SHIVC, IHIVC and PoV was 2.5 (range, 0-10), 0(0-5), 9(0-31), 0(0-6) and 1(0-5), respectively. Patients with satellite lesions were associated with more CTCs in PV and PA (P<0.05). Mean sizes of CTCs measured in SHIVC were significantly larger than those measured in PV and PA (P<0.001). Majority of CTCs in SHIVC were scored strong cytokeratin (CK) expression, whereas CTCs scored weak and moderate CK expression were more frequently observed in PV and PA. SHIVC contained a higher number of circulating tumor microemboli (CTM) than the other vascular sites. Surgical procedures except percutaneous RFA led to a significant fall of CTCs within 24 hours after treatment, while all surgical procedures were associated with a significant decrease of CTCs 1 month after treatment. Open surgery led to an increase of CTC 1 week after surgery, whereas CTC level kept decreasing after laparoscopic surgery. Conclusions: A greater number of CTCs and CTMs were detected in SHIVC, explaining why lungs were the most frequent metastatic destination of HCC. Filtration of CTCs at SHIVC might be a promising therapeutic option for preventing the occurrence of HCC metastasis. CTCs appeared to undergo a dynamic down-regulation of epithelial-marker expression during their circulating in bloodstream. Minimal-invasive procedures of laparoscopic surgery contributed to less CTC releasing, which might reduce the risk of recurrence and metastasis.
Incidence of advanced prostate cancer in men under the age of 50 in the United States: A population-based study 1973-2010.
Authors: Uladzislau Naidzionak, Katsiaryna Ivanova, Akm Mosharraf Hossain
Journal: Journal of Clinical Oncology (2014)

e16030 Background: Prostate cancer (PC) is the most common non-cutaneous cancer in males in United States. Escalating incidence rate (IR) of PC noted in the last two decades was attributed to more common use of PSA testing for early PC detection. The aim of our study is to compare the relative and absolute rates of detection of early and advanced PC in younger males under the age of 50 and to examine if early cancer was the only contributor to the change in this group. Methods: Frequency and rate sessions on demographics and PC characteristics were performed and compared among Non-Hispanic White (NHW), African-American (AA), Hispanic (H), US Asian/Pacific Islanders (A/PI) and American Indians/Alaskan Natives (AI/AN) using SEER*Stat. IR and stage at diagnosis trends were examined with subjects diagnosed under the age of 50 years. Survival sessions (Kaplan-Meier, age adjusted) was performed using SEER database from 1973 to 2010. Results: A total of 22,227 cases of PC were reported under the age of 50 years at diagnosis in SEER database from 1973-2010. About 77% were in NHW, 12% in AA, 6% in Hispanics, 4% in A/PI and less than 1% in AI/AN. Table below reflects our results. Conclusions: IR of PC increased significantly in the last decade in men of all races under the age of 50. However stage breakdown did not change significantly. This implies that incidence of advanced stages prostate cancer escalated in parallel with early stages. This increase can’t be fully explained by the use of PSA screening. We propose that aforementioned phenomenon may be related to unknown epigenetic, environmental or socioeconomic factors. Relative increase in IR was especially high in A/PI (by 125%) with a trend towards increase of advanced stage cancer share (by 3%). Further studies into PC risk factors are warranted. Year Variables NHW AA H A/PI AI/AN 2000 Incidence rate per 100,000 2.0 4.8 1.2 0.4 0.5 Early stages (I/II) % 63 58 62 65 57 Advanced stages (III/IV) % 37 42 38 35 43 2005 Incidence rate per 100,000 2.4 5.8 1.6 0.7 0.9 Early stages (I/II) % 62 60 64 63 60 Advanced stages (III/IV) % 38 40 36 37 40 2010 Incidence rate per 100,000 2.8 6.9 1.9 0.9 1.2 Early stages (I/II) % 65 61 65 62 59 Advanced stages (III/IV) % 35 39 35 38 41
TIM-3 Expression on CD4+ Bone Marrow T Cells Predicts Relapse of Pediatric B-Precursor Acute Lymphoblastic Leukemia
Authors: Franziska Blaeschke, Semjon Willier, Dana Stenger, Mareike Lepenies, Martin A. Horstmann, Gabriele Escherich, Martin Zimmermann, Theresa Kaeuferle, Meino Rohlfs, Irene Schmid, Michael H. Albert, Vera Binder, Christoph Klein, Tobias Feuchtinger
Journal: Blood (2018)
Abstract P379: Leg Length, Marker of Environmental Exposition During Early Lifetime, and Subclinical Cardiovascular Disease
Authors: Xiomara Alba, Dalia Stern, Karl Puchner, Eduardo Ortiz, Elsa Yunes, Carlos Cantú-Brito, Jorge Zuñiga, Martin Lajous, Ruy L. Ridaura
Journal: Circulation (2017)

Introduction: Intrauterine and early life factors such as low birth weight, not being breastfed, smoking parents, and other socioeconomic conditions have been associated with later predisposition to chronic diseases. Although there still exists controversy in which is the best marker for environmental exposition during early lifetime, leg length has been one of the most accepted. Hypothesis: There is an inverse relationship between leg length and subclinical cardiovascular disease (sCVD). Methods: We conducted a cross-sectional analysis of a sub sample of 2,038 women from the Mexican Teacher’s Cohort. Participants underwent anthropometry during clinical assessments. Trunk length was calculated as the height measured in seated position minus the height of the stool participants were sitting on. Leg length was defined as height minus trunk length. Carotid intima media thickness(CIMT) was measured by trained neurologists through standardized ultrasound and log-transformed. We defined sCVD as CIMT ≥0.8 mm or the presence of plaque. We used multivariable linear and logistic regression models to estimate the association between leg length quartiles with CIMT and sCVD respectively. Results: Mean height was 153.8 cm and mean leg length was 72 cm. The prevalence of sCVD was 23%(469 of 2038). Participants with shorter legs were likely to report low birthweight, indigenous origin, rural residence, and low socioeconomic environment. We observed an inverse relationship between leg length and mean IMT when we compared the lowest(median 67cm) to the highest quartile(median 77.1 cm) ( multivariable-adjusted mean % difference= -2.93; 95% CI-5.53,-0.32 ). In contrast to the lowest quartile, the multiple-adjusted odds ratio for sCVD in the highest quartile was 0.58( 95% CI 0.34, 0.98 ). Additional analysis controlling for mediators such as weight, diabetes, hypertension and hypercholesterolemia weakened the association but remained significant. Conclusion: We found a significant association between leg length, CIMT and sCVD in a population of middle-aged Mexican women.