tbuckley/cabot-search huggingface dataset:
Combined biological treatment and chemotherapy for patients with inoperable cholangiocarcinoma.
Authors: L. H. Jensen, U. N. Lassen, J. Lindebjerg, T. Hansen, A. K. Jakobsen
Journal: Journal of Clinical Oncology (2010)

TPS217 Background: Cholangiocarcinoma (CC) is a relatively rare cancer with a severe prognosis. There are no standard chemotherapy to offer incurable patients, but regimes combining cisplatin and gemcitabine are commonly used based on preliminary phase III data. In Denmark, a combination of gemcitabine, oxaliplatin and capecitabine has been evaluated in phase I and phase II trials. Based on experience with other gastrointestinal tumors, there seems to be an additional effect when combining chemotherapy and epithelial growth factor receptor (EGFR) antibodies. Effect of EGFR inhibitors is only seen if the down-stream signalling protein KRAS is not mutated. 50% of CC are expected to hold KRAS mutations. The purpose of the trial is to evaluate the specific anti-tumor effect of (i) chemotherapy and panitumumab in CC without KRAS mutations and (ii) chemotherapy alone in patients with KRAS mutations. Methods: Eligibility criteria are made to reflect daily clinical practice and diminish selection bias by allowing inclusion of patients with performance status 2, age up to 80 years, and evaluable (not necessarily measurable) disease. Furthermore, histopathology only needs to be consistent with adenocarcinoma arisen from bile ducts together with a radiologic diagnosis of CC. The study is designed as two parallel phase II trials selected by KRAS status. In each trial a two-stage design is chosen with inclusion of 15-18 patients in stage one and 25-33 patients in stage II. All patients receive gemcitabine 1000 mg/m2 and oxaliplatin 60 mg/m2 on day one plus capecitabine 1000 mg/m2 b.i.d. day one to seven on a two weeks cycle. If KRAS wild-type panitumumab 6 mg/kg is given day one. The primary endpoint is progression free survival and secondary endpoints response rate, toxicity, and overall survival. During the trial tumor tissue and regular blood tests are collected for future translational research. Accrual began in September 2008 and is considerably higher in the panitumumab group, where the last patient is expected to be included in mid-2010. Surprisingly, only 5-10% have KRAS mutation and this part of the study will continue longer. Results will be reported separately. No significant financial relationships to disclose.
Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study
Authors: Tai-Ming Ko, Chang-Youh Tsai, Shih-Yang Chen, Kuo-Shu Chen, Kuang-Hui Yu, Chih-Sheng Chu, Chung-Ming Huang, Chrong-Reen Wang, Chia-Tse Weng, Chia-Li Yu, Song-Chou Hsieh, Jer-Chia Tsai, Wen-Ter Lai, Wen-Chan Tsai, Guang-Dar Yin, Tsan-Teng Ou, Kai-Hung Cheng, Jeng-Hsien Yen, Teh-Ling Liou, Tsung-Hsien Lin, Der-Yuan Chen, Pi-Jung Hsiao, Meng-Yu Weng, Yi-Ming Chen, Chen-Hung Chen, Ming-Fei Liu, Hsueh-Wei Yen, Jia-Jung Lee, Mei-Chuan Kuo, Chen-Ching Wu, Shih-Yuan Hung, Shue-Fen Luo, Ya-Hui Yang, Hui-Ping Chuang, Yi-Chun Chou, Hung-Ting Liao, Chia-Wen Wang, Chun-Lin Huang, Chia-Shuo Chang, Ming-Ta Michael Lee, Pei Chen, Chih-Shung Wong, Chien-Hsiun Chen, Jer-Yuarn Wu, Yuan-Tsong Chen, Chen-Yang Shen
Journal: BMJ (2015)

<b>Objective</b> To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. <b>Design</b> National prospective cohort study. <b>Setting</b> 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. <b>Participants</b> 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B*58:01. <b>Main outcome measures</b> Incidence of allopurinol induced SCARs with and without screening. <b>Results</b> Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). <b>Conclusions</b> Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.
Cigarette Smoking Induces Changes in Airway Epithelial Expression of Genes Associated with Monogenic Lung Disorders
Authors: Ann E. Tilley, Michelle R. Staudt, Jacqueline Salit, Benjamin Van de Graaf, Yael Strulovici-Barel, Robert J. Kaner, Thomas Vincent, Francisco Agosto-Perez, Jason G. Mezey, Benjamin A. Raby, Ronald G. Crystal
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Busulfan plus cyclophosphamide followed by autologous blood stem-cell transplantation for patients with acute myeloblastic leukemia in first complete remission: a report from a single institution.
Authors: M A Sanz, J de la Rubia, G F Sanz, G Martín, J Martínez, I Jarque, A Sempere, F Gomis, L Senent, M A Soler
Journal: Journal of Clinical Oncology (1993)

To determine if peripheral-blood stem cells (PBSC) collected during the recovery of standard induction and consolidation chemotherapy in acute myeloblastic leukemia (AML) can be used as a safe tool for autologous transplantation, and to study aspects of the autologous blood stem-cell transplantation (ABSCT) procedure and their results in AML patients in first remission.Twenty-four AML patients in first remission received busulfan (BU; 16 mg/kg) and cyclophosphamide (CY; 200 mg/kg) followed by ABSCT. PBSC were collected by continuous-flow leukaphereses after induction and consolidation courses.The median numbers of mononuclear cells (MNCs) and colony-forming unit granulocyte-macrophage (CFU-GM) administered were 6 x 10(8)/kg and 11 x 10(4)/kg, respectively. ABSCT induced engraftment in 22 patients and there were two graft failures. The median times to reach a polymorphonuclear (PMN) leukocyte count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L were 13 and 19 days, respectively. Fatal hepatic veno-occlusive disease (VOD) was observed in two cases. Other toxicities were mild and uncommon. Twelve patients relapsed between 1 and 9 months posttreatment. Actuarial disease-free survival (DFS) and actuarial risk of relapse at 30 months were 35% (95% confidence interval [CI], 25% to 45%) and 60% (95% CI, 50% to 72%), respectively.These preliminary results show the fast hematopoietic recovery and the low infectious and hemorrhagic morbidity associated with the procedure and strongly suggest that ABSCT may be as effective as autologous bone marrow transplantation (ABMT) in AML. However, further strategies for reducing leukemic relapse must still be investigated.
P-143 Weight Loss during chemotherapy in patients with advanced Oesophagogastric (OG) and Hepatobiliary-Pancreatic (HPB) cancers is not a surrogate for disease progression
Authors: G. Oikonomopoulos, S. Payne, S. Ngan, S. Chosdhury, M. Hession, D. AlRifai, D. Sarker, P. Ross, N. Maisey
Journal: Annals of Oncology (2015)
Microtubules mediate anti-inflammatory and lung vascular barrier protective effects of atrial natriuretic peptide
Authors: Anna Birukova, Alok Shah, Yufeng Tian, Fanyoung Meng
Journal: European Respiratory Journal (2014)

Independently on control of circulating fluid, atrial natriuretic peptide (ANP) exhibits anti-inflammatory effects in the lung. We tested a role of microtubule (MT) cytoskeleton in the ANP-induced protection against endothelial cell (EC) barrier dysfunction and acute lung injury induced by  Staphylococcus aureus -derived peptidoglican-G (PepG). ANP attenuated PepG-induced Rho signaling via suppression of PepG-induced MT disassembly and inhibition of MT-associated Rho-specific guanine nucleotide exchange factor GEF-H1. ANP-induced EC barrier preservation and MT stabilization was due to phosphorylation and inactivation of MT-associated protein stathmin. Phosphorylation deficient stathmin-S63A mutant abolished ANP protective effects against PepG-induced hyperpermeability, activation of Rho and NFkB signaling, and expression of inflammatory adhesion molecules. In contrast, siRNA-based stathmin knockdown prevented PepG-induced peripheral MT disassembly and EC barrier dysfunction. ANP protective effects in murine model of PepG-induced lung injury were associated with increased acetylated MT and phospho-stathmin levels, while exacerbated lung injury in the ANP knockout mice was accompanied by decreased pool of stable MT. Stathmin knockdown  in vivo  reversed exacerbation of lung injury in ANP knockout mice. These results show a novel mechanism of EC barrier protection and mitigation of inflammation by ANP in EC culture and in the  in vivo  model of lung injury via stathmin-dependent MT assembly and MT-regulated Rho signaling.   Funding:  HL087823, HL107920.
Predictors of site-specific recurrence following combined modality therapy for locally advanced rectal cancer.
Authors: P. Ding, D. Liska, K. A. Goodman, L. Saltz, J. G. Guillem, P. Paty, L. K. Temple, G. M. Nash, W. D. Wong, M. R. Weiser
Journal: Journal of Clinical Oncology (2010)

3642 Background: The aim of this study is to identify factors associated with site specific recurrence in patients with locally advanced rectal cancer treated by combined modality therapy (CMT): neoadjuvant chemoradiation followed by total mesorectal excision. Methods: From a prospectively maintained single institution database we identified 593 consecutive locally advanced (uT3 or uN1) rectal cancer patients staged by endorectal ultrasound and treated with CMT from 1998-2007. Univariate and multivariate analyses were performed to identify risk factors associated with all- site and organ specific recurrence-free survival (RFS). Results: After median follow-up of 44 months, 119 patients (20%) recurred. The most common single site recurrences were lung in 59 patients (69%) and liver in 13 (15%). On multivariate analysis, pathologic stage (ypTNM), tumor location (from anal verge), and lymphovascular or perineural invasion (LVI or PNI) were significantly associated with all-site and pulmonary-specific RFS (Table). 5-year RFS for patients with 0, 1, 2, and 3 of the identified risk factors was 96%, 78%, 43%, and 24%, respectively. Circumferentialresection margin (CRM) status and ypTNM stage were the only independent predictors for local and liver-specific RFS, respectively. Conclusions: Lung is the most common site of recurrence following CMT for locally advanced rectal cancer. Tumor location, ypTNM stage, and presence of LVI or PNI are associated with all-site and pulmonary-specific recurrence. The identified factors and associated model may aid in risk-adaptive therapeutic and surveillance strategies. Multivariate model predicting all-site and pulmonary-specific recurrence Features All-site recurrence Pulmonary recurrence P Hazard ratio (CI) P Hazard ratio (CI) Location from AV <0.001 2.38 (1.59-3.57) 2.38 (1.35-4.17) (≤5 vs. >5 cm) <0.005 ypTNM (II /III vs. 0/I) <0.001 5.10 (2.89-9.00) <0.001 4.70 (2.03-10.84) LVI or PNI (+ vs. -) <0.001 2.05 (1.38-3.04) <0.001 3.58 (2.05-6.25) No significant financial relationships to disclose.
Pegfilgrastim in colorectal cancer (CRC) patients (pts) receiving every-two-week (Q2W) chemotherapy (CT): Long-term results from a phase II, randomized, controlled study
Authors: J. R. Hecht, M. Pillai, R. Gollard, L. Dreiling, M. Mo, I. Malik
Journal: Journal of Clinical Oncology (2009)

4072 Background: Survival in advanced CRC is prolonged by adding oxaliplatin (Ox) and/or irinotecan (Iri) to Q2W 5-fluorouracil/leucovorin (5FU/LV). Combination therapy, however, has a higher incidence of febrile neutropenia (FN) and related toxicities. This study evaluated pegfilgrastim dosing on day 4 of Q2W regimens in CRC. Here we present long-term follow-up of these pts. Methods: Advanced CRC pts were randomized (1:1) to pegfilgrastim 6mg or placebo, which was stratified by CT regimen received: FOIL, FOLFOX, or FOLFIRI. We previously reported grade 3/4 neutropenia (primary endpoint) in 43% placebo and 13% pegfilgrastim pts in the 4-cycle treatment phase (odds ratio = 0.19, 95% CI: 0.10–0.37; p &lt; 0.0001). After end of treatment, pts were followed long term for ≤ 2 years (inclusive of ≤ 8 additional cycles) for serious adverse events (SAEs), overall survival (OS), and progression-free survival (PFS). Median follow-up time was 519 days. Kaplan-Meier methods estimated OS and PFS from study day 1. The study was not powered to detect PFS or OS differences between treatment groups. Results: Of 241 pts analyzed (123 pegfilgrastim, 118 placebo), 49% received FOLFOX, 26% FOLFIRI, and 25% FOIL. In the treatment period, 8% placebo and 2% pegfilgrastim pts had grade 3/4 FN ( Table ). Pegfilgrastim was well tolerated with no dose delays attributed to leukocytosis. Pegfilgrastim and placebo had similar PFS and OS ( Table ). No SAEs related to study drug were reported in the follow-up period. Conclusions: In this randomized, placebo-controlled study, pegfilgrastim significantly lowered neutropenic risk. Bone pain incidence in this CRC population was lower than in breast cancer pts treated with a taxane (Vogel J Clin Oncol 2005); the incidence in pegfilgrastim pts was modestly increased over placebo. Leukocytosis was not a concern despite the 11-day dosing interval. Long-term results suggest similar PFS and OS in the pegfilgrastim and placebo pts in this CRC study. [Table: see text] [Table: see text]
Depletion of Alloreactive T Cells by a Specific Anti–Interleukin-2 Receptor p55 Chain Immunotoxin Does Not Impair In Vitro Antileukemia and Antiviral Activity
Authors: Daniela Montagna, Eric Yvon, Valeria Calcaterra, Patrizia Comoli, Franco Locatelli, Rita Maccario, Alain Fisher, Marina Cavazzana-Calvo
Journal: Blood (1999)
Non-Hodgkin's lymphoma arising in skeletal muscle
Authors: G.M. Jeffery, P.F. Golding, G.M. Mead
Journal: Annals of Oncology (1991)

Four patients with non-Hodgkin's lymphoma who presented with clinical enlargement of muscle are reported. In three patients the only site of disease was muscle. Two patients with involvement of the paraspinal muscles demonstrated neurological complications due to spinal nerve root entrapment. A review of the literature emphasises the rarity of primary muscle lymphoma and suggests that disease arising at this site may confer a poor prognosis.
A phase I study of uracil/tegafur (UFT) and oral leucovorin (LV) + weekly oxaliplatin (OXA) and preoperative radiotherapy (RT) in locally advanced rectal cancer (LARC)
Authors: C. Aschele, M. L. Vitali, G. A. Binda, F. Decian, G. Battistini, C. Caroti, M. D' Amico, P. Ricci, A. Siragusa, L. Gallo
Journal: Journal of Clinical Oncology (2004)

3637 Background: We have recently demonstrated that OXA, given weekly at the dose of 60 mg/m2, may be safely combined with infusional FU and preoperative pelvic RT for LARC resulting in rates of pathological complete responses (pCR's) approaching 30 %. Replacing infusional FU with an oral fluoropyrimidine might reduce the inconvenience and some of the potential complications of this regimen. Methods: Since June 2002, 15 patients (10 males, 5 females; median age 63, range 33–75 years) with LARC (cT3-T4 and/or N+; one patient also had a potentially resectable liver metastasis) were thus accrued in a phase I study aimed at defining the maximum tolerated dose (MTD) of UFT (200–250-300–350 mg/m2/day, monday through friday for all the duration of RT) combined with weekly OXA (60 mg/m2) and standard pelvic RT (50.4 Gy - 28 fractions). Oral LV (90 mg/day, fixed dose) was administered with the same schedule as UFT. Results: No grade III-IV toxicity was observed at the first dose level (n=4; UFT 200 mg/m2/day). At the second dose level (UFT 250 mg/m2/day), one patient discontinued treatment because of protracted severe obtundation. This cohort was thus expanded (n=6) without any other grade 3–4 toxicity or major deviation from the planned treatment. All the patients accrued at the third dose level (n=5; UFT 300 mg/m2/day) completed treatment as planned without any grade III-IV toxicity. Two patients were not operated due to progression of extrapelvic disease while one patient with a clinical complete response refused surgery and one has just completed chemoradiation and is waiting for operation. Among 11 patients for whom final pathologic reports are available, 2 pCR's were reported and 3 patients were staged as pT1–2N0. Conclusions: These results demonstrate that oral UFT may replace infusional FU in combination with weekly OXA and standard pelvic RT with low toxicity and without reaching the MTD up to the dose of 300 mg/m2/day. pCR's were obtained providing preliminary evidence of high antitumor activity. The study is now accruing patients at UFT 350 mg/m2/day (last dose level). No significant financial relationships to disclose.
Evaluation of Ki-67 in gastrointestinal stromal tumor (GIST)
Authors: M. Saponara, M. Di Battista, C. Lolli, E. Derenzini, M. A. Pantaleo, D. Santini, C. Ceccarelli, F. Catena, M. Nannini, A. Maleddu, G. Biasco
Journal: Journal of Clinical Oncology (2009)

e21510 Background: GISTs show a wide spectrum of biological behaviors which translates in an even wider spectrum of possible clinical courses. The two canonical parameters used for the prediction of GISTs’ prognosis are tumor size and mitotic index. However, few but controversial data on Ki-67 are also available. The aim of our study was to clarify the role of Ki-67 expression as a new biological marker in GISTs. Methods: Forty-one cases of GIST were examined. Twenty-six cases arose from stomach and 15 from small bowel. Immunohistochemical analysis for Ki-67 was stained on tissue samples and a cut-off value of &gt;10% immunoreactive cells was used to distinguish between low (&lt;= 10%) and high (&gt;10%) Ki-67 nuclear expression. The expression of this cell-cycle related protein was correlated with tumor site (stomach; any other site), dimensions (&lt;5 cm; &gt;=5cm), mitotic index (&lt;=5/50 HPFs; &gt;5/50 HPFs), standard risk groups (low; intermediate-high) and disease free survival (DFS). Results: Ki-67 over-expression was positively correlated with tumor size &gt;=5cm (p= 0.035). Not significant but a positive trend was seen with intermediate and high risk groups (p = 0.114), mitotic index &gt;5/50 HPFs (p = 0.615). Lower levels of Ki-67 expression have been observed in gastric GISTs compared to any other site (29 cases with Ki-67 &lt;=10% of which 21 gastric and 8 in other sites), even if these values were not statistically significant (p = 0.527). Moreover, Ki-67 over-expression was found to be significantly associated with a shorter DFS interval (p = 0.0196, analysis performed on 32 cases). Conclusions: Our data demonstrate that Ki-67 over-expression is significantly correlated with larger GIST and with a shorter DFS, suggesting that Ki-67 evaluation can be a useful tool to predict biological behavior of GIST, even if further studies are needed. In a clinical perspective, such information could be used in association with standard risk factors to select patients who could benefit from adjuvant therapy. No significant financial relationships to disclose.
Post-operative conformal radiotherapy on prostate cancer after radical prostatectomy. Results and dose constraint on bladder volume
Authors: R. A. Nakamura, C. R. Monti, R. Ferrigno, F. A. Trevisan, L. N. Castilho, J. A. Reinato
Journal: Journal of Clinical Oncology (2006)

14647 Background: To report on the results of post-operative conformal radiotherapy (3DCRT) on patients submitted to radical prostatectomy with high risk of biochemical failure or with biochemical failure. Methods: From July 1998 to December 2001, 40 patients with high risk of biochemical failure (T3 stage or positive margins) or with biochemical failure (PSA ≥ 0.2 ng/ml) after radical prostatectomy were submitted to 3DCRT on a single institution and were analyzed retrospectively. The median age was 65 years (52–74). The median pre-3DCRT PSA was 1.3 ng/ml (0–8.98). Twenty eight patients were submitted to pelvic 3DCRT. The median radiation dose on prostate region was 77 Gy (68.4–81). Biochemical failure was considered after 3 consecutive PSA increasing or the beginning of androgen suppression therapy for any reason after 3DCRT. Results: The median follow-up was 56.1 months (19.7–84.6). The 5-year actuarial biochemical progression-free survival was 84.5%. Six (15%) patients had biochemical failure and 4 (10%) distant metastases. The 5-year actuarial biochemical progression-free survival was 94.9% with pre-3DCRT PSA ≤1.5 ng/ml and 69.9% when &gt;1.5 ng/ml (p = 0.0215). Two patients had rectal bleeding grade 2. Nine patients had urinary toxicity grade 2–3. The 5-year actuarial free from urinary toxicity grade 2–3 was 72.9%. Age &gt;65 years and radiation dose &gt;65 Gy on 30% of bladder volume resulted on more late urinary toxicity grade 2–3 (p = 0.0410 and p = 0.0177, respectively). Conclusions: 3DCRT was effective for biochemical control on patients with high risk of biochemical failure or with biochemical failure after radical prostatectomy. Patients with pre-3DCRT PSA ≤1.5 ng/ml have more biochemical control. It was suggested to restrict radiation dose ≤65 Gy on 30% of bladder volume to minimize late grade 2–3 urinary toxicity. More cautious on patients &gt;65 years submitted to post-operative irradiation are required. No significant financial relationships to disclose.