tbuckley/cabot-search huggingface dataset:
A phase I dose-escalating study of combination S-1 and carboplatin (CBDCA) in patients with chemo-naïve advanced non-small cell lung cancer (NSCLC)
Authors: K. Tamura, I. Okamoto, T. Ozaki, T. Shimizu, T. Kashii, K. Takeda, K. Matsui, S. Kudoh, T. Kurata, M. Fukuoka
Journal: Journal of Clinical Oncology (2006)

17055 Background: S1, a novel oral fluoropyrimidine derivative, has promising results in the treatment of advanced gastric or colorectal carcinoma. Response rate/median survival time of single S1 and the combination S1 plus cisplatin for advanced NSCLC were 22.0%/309 days and 47.3%/335 days, respectively in the previous phase II. Platinum doublets including a novel active drug is a potent standard for advanced NSCLC as 1 st line chemotherapy. Carboplatin has advantage of low gastrointestinal or renal dysfunction in comparison with cisplatin. The primary objective of this study was to determine the maximum tolerated dose (MTD) of combination S-1 and carboplatin, the toxicity profile and the recommend dose (RD) for a multi-center randomized trial of platinum doublets including S1. Methods: Eligibility criteria includes histologically diagnosed NSCLC stage IIIB/IV, no prior chemotherapy, ECOG PS 0–1, 75 &gt; age &gt;20, adequate organ function, and written informed consent. Pts receive carboplatin intravenously over 30 minutes on day 1, and S1 daily for 2 weeks, every 3 weeks. Results: Total 10 patients were registered (M/F: 6/4; median age:67 (37–73); Ad/Sq:7/3; IIIB/IV: 0/10 PS 0/1:3/7) Three patients were enrolled at the dose level 1 (CBDCA AUC = 5 and S1 65 mg/m 2 ), 3 patients at level 2 (CBDCA AUC=5 and S1 80 mg/m 2 ) and 4 patients at level 3 (CBDCA AUC=6 and S1 80 mg/m 2 ), respectively. No DLTs (dose-limiting toxicities) occurred at both level 1 and 2. DLTs were observed in 2 out of 4 patients at level 3. One is significant delay starting of 2 nd cycle caused by thrombocytopenia. One is G3 anorexia and vomiting at 1 st cycle and results in stop the treatment. A total 27 courses were assessable for safety. Two pts with G3 neutropenia, 2 pts with G3 anorexia, 1 pts with G3 liver dysfunction and 1 pts with G3 infection were observed during total courses. Five out of 6 patients at Level 1 or 2 have completion of 4 cycle’s treatment. Objective response was obtained in three patients out of 10. Conclusions: MTD was level 3. RD for the future trial was Level 2 (CBDCA AUC = 5 and S1 80 mg/m 2 ). This combination was well tolerated and produced an antitumor effect for advanced NSCLC. No significant financial relationships to disclose.
Association between cigarette smoking and suicide in psychiatric inpatients
Authors: Hooman Sharifi Milani, Zahra Hessami, Mohammad Reza Masjedi
Journal: European Respiratory Journal (2013)

Introduction:   Cigarette smoking is the single largest preventable cause of death and disability in the industrialized world and it causes at least 85% of lung cancers, chronic bronchitis and emphysema. In addition smokers are at a higher risk from psychiatric co-morbid illness such as depression and completed suicide.   Methods:   We conducted a cross-sectional survey in which we targeted all patients with serious mental illness (SMI) who were admitted in Razi mental health Hospital in Tehran, Iran. We recruited 984 participants, who were receiving services from Razi mental health Hospital and hospitalized for at least two days between 21 July to 21 September, 2010. Nine hundred and fifty patients out of this figure were able to participate in our study.   Results:   The final study sample (n = 950) consisted of 73.2% males and 26.8% females. The mean age was 45.31 (SD=13.7). A majority of participants (70%) was smoker. A history of never smoking was present for 25.2% of the study sample; while 4.8% qualified as former smokers and 70.0% as occasional or current smokers. Two hundred and nineteen participants had attempted suicide amongst them 102 (46.6%) once, 37 (16.9%) twice, and 80 (36.5%) attempted more than two times in their life time. In regression model, gender, age, and cigarette consumption were associated with previous suicide attempts and entered the model in this order as significant predictors.   Conclusion:   There is an association of cigarette smoking and suicide attempt in psychiatric inpatients. Current smoking, a simple clinical assessment, should trigger greater attention by clinicians to potential suicidality and become part of a comprehensive assessment of suicide risk.
BI 836845, a fully human IGF ligand neutralizing antibody, to improve the efficacy of rapamycin by blocking rapamycin-induced AKT activation.
Authors: Paul J. Adam, Katrin Friedbichler, Marco H. Hofmann, Thomas Bogenrieder, Eric Borges, Guenther R. Adolf
Journal: Journal of Clinical Oncology (2012)

3092 Background: Analogs of rapamycin (rapalogs) targeting mammalian target of rapamycin complex 1 (mTORC1) have shown clinical activity in several cancers. Nonetheless, preclinical and clinical data suggest that there may be intrinsic resistance to rapalogs through a feedback loop which activates upstream signaling when mTORC1 is blocked. BI 836845 is a fully human antibody, currently in phase I clinical trials, which potently neutralizes both IGF-1 and IGF-2. We tested whether BI 836845 is able to improve the efficacy of rapamycin by inhibiting upstream signaling in preclinical models. Methods: Cancer cell lines were profiled in vitro and in vivo for sensitivity to BI 836845 and rapamycin, alone or in combination. Mitogenic signaling was examined by measuring levels of phosphorylated AKT (pAKT) using Western blot analysis. IGF bioactivity was determined using a cellular IGF-1R phosphorylation ELISA. Results: The combination of BI 836845 and rapamycin was more effective than either agent alone at inhibiting the proliferation of Ewing’s sarcoma cells cultured in vitro as well as in a nude mouse xenograft model in vivo. Analysis of cell signaling upstream of mTOR demonstrated that treatment with rapamycin alone resulted in elevated pAKT, indicating feedback loop activation. BI 836845 treatment alone or in combination with rapamycin inhibited AKT phosphorylation, demonstrating that the rapamycin-induced increase in pAKT was due to elevated IGF bioactivity. Consistent with this we demonstrated that rapamycin increased IGF bioactivity in mice and that this could be inhibited by BI 836845. We extended these studies to include other cancer cell lines and profiled the correlation between improved efficacy of the combination with BI 836845 inhibition of rapamycin-induced feedback. A correlation has been observed for cancer cells derived from several indications. Conclusions: Rapamycin treatment increases AKT activation via elevated IGF ligand bioactivity. This effect can be inhibited by BI 836845, thus explaining the improved pre-clinical efficacy seen when both agents are combined. These data provide a rationale for the clinical combination of rapalogs and BI 836845.
Clinical Outcomes and Mutation Clearance in Children with Acute Myeloid Leukemia Treated with Low-Dose Chemotherapy Plus G-CSF for Remission Induction
Authors: Aili Chen, Yixin Hu, Xinchang Zheng, Jun Lu, Peifang Xiao, Jin Yang, Ya Zhang, Pinpin Sui, Jingyi Yang, Fuhong He, Hailong He, Yi Wang, Chung-I Wu, Xin Liu, Yinmei Zhou, Deqing Pei, Cheng Cheng, Raul C. Ribeiro, Shaoyan Hu, Qianfei Wang
Journal: Blood (2017)
A pilot study of sleep-related breathing disorders and hypersomnia in adult survivors of childhood Hodgkin lymphoma treated with thoracic radiation.
Authors: Belinda Neal Mandrell, William Lewis, Susan Ogg, Merrill Wise, Daniel A. Mulrooney, Leslie L. Robison, Melissa M. Hudson, Kevin R. Krull
Journal: Journal of Clinical Oncology (2019)

e21527 Background: Survivors of childhood Hodgkin lymphoma (HL) often report fatigue and daytime sleepiness. The presence of sleep disorders, such as obstructive sleep apnea (OSA), could further increase cardiovascular and cerebrovascular morbidity and mortality in these patients. The purpose of this pilot study was to assess for the presence of sleep-related breathing disorders and hypersomnia in adult survivors of childhood HL treated with thoracic radiation. Methods: Survivors, ≥18 years of age and ≥10 years from diagnosis, were randomly selected from the St. Jude Lifetime Cohort (SJLIFE) study and assessed with nocturnal polysomnography (PSG) and the multiple sleep latency test (MSLT). Enrollment was stratified by body mass index (BMI) to include an equal number of normal weight and overweight/obese survivors. Survivors with a history of neurotoxicity related to cancer therapies, and neurological, genetic, or neurodevelopmental conditions associated with neurocognitive impairment were excluded. Results: Thirty adult survivors of childhood HL (60% male; 73% white; mean age 35.8 years [range,19.9-52.8]; BMI 28.6 [range, 18.2-43.5]) enrolled, and 14 (47%) met PSG criteria for mild or moderate OSA (OSA; apnea-hypopnea index 5-30). Of those with OSA, 11 had concurrent hypersomnia using the MSLT criteria and 3 of these 11 met diagnostic criteria for narcolepsy. Twelve (40%) had hypersomnia without OSA and 3 of these 12 met diagnostic criteria for narcolepsy. Within the cohort, 86% had objective evidence of OSA and/or hypersomnia/narcolepsy. Conclusions: Findings suggest adult survivors of childhood HL may be at increased risk for OSA, which when concurrent with treatment-related cardiopulmonary and cerebrovascular risk may further increase morbidity and mortality. Future studies are warranted to compare the prevalence of OSA in this population with a matched community control group and examine whether and how the mechanism for OSA might differ from that in the general population.
Abstract 15542: Congenitally Corrected Transposition of the Great Arteries Presenting in the First Year of Life: Survival and Long Term Fate of the Systemic Right Ventricle
Authors: Benjamin Smood, James K Kirklin, Jozef Pavnica, Margaret Tresler, Walter Johnson, Robert Dabal, David Mauchley, David Cleveland
Journal: Circulation (2017)

Introduction: Life expectancy and functional outcome of patients with congenitally corrected transposition of the great arteries (ccTGA) presenting early in life remains incompletely understood. In...
Phase I and pharmacokinetic evaluation of enzastaurin combined with gemcitabine and cisplatin in advanced cancer
Authors: L. Beerepoot, J. Rademaker-Lakhai, E. Witteveen, S. Radema, C. Viseren-Grul, L. Musib, J. Van Hal, J. Beijnen, J. Schellens, E. Voest
Journal: Journal of Clinical Oncology (2006)

2046 Background: Enzastaurin (Enz), an oral PKC inhibitor that also suppresses PI3K/AKT pathways, blocks tumor angiogenesis and tumor cell proliferation and induces tumor cell death. Gemcitabine (Gem) and cisplatin (Cis) combination is often used for treatment of solid tumors. Addition of Enz to the regimen has the potential for enhanced clinical benefits without increasing toxicity. Methods: In this phase I, dose-escalation trial, patients (pts) with advanced, refractory, solid tumors received a lead-in treatment (cycle 1) with oral Enz for 14 days to achieve steady-state exposures. Starting with cycle 2, pts received Enz orally (350 mg qd to 500 mg bid) on days 1–21 combined with Gem (1000 or 1250 mg/m 2 ) as a 30-min iv infusion on days 1,8 and Cis (60 or 75 mg/m 2 ) as a 3-h iv infusion on day 1, every 21 days, for up to 7 cycles. Results: 33 pts (22 males, 11 females; ECOG: 0–2), with a median age of 58 yrs (range: 38–79 yrs), were enrolled in 7 dose levels. The MTD was not identified. Two DLTs were reported, 1 grade (Gr) 2 QTc interval prolongation and 1 Gr 3 fatigue, both during cycle 1 in bid cohorts. Laboratory toxicities included Gr 3/4 neutropenia (3/6 pts), thrombocytopenia (1/6 pts), and Gr 3 leukopenia (2 pts), hyperglycemia (1 pt), and creatinine (1 pt). Gr 3 toxicity reported in &gt;1 pt was fatigue (5 pts). Enz bid (≥ 250 mg bid) was associated with more discontinuations in early cycles, more Enz dose adjustments, higher numbers of possibly-related SAEs, and increased numbers of low-grade CTC toxicities compared to the corresponding qd dosing. Exposures of Enz in the presence of Gem and Cis decreased slightly but the decrease was not clinically significant as the mean exposure remained above the targeted exposure of 1400 nM. Gem and Cis exposures were not altered when given in combination with enz, as compared to historical data. Of 24 evaluable pts, 3 pts (pancreatic, head/neck, and ovarian cancer) achieved a partial response, whereas 13 achieved stable disease for ≥ 2 cycles. Conclusions: Based on safety and PK data, the recommended phase II dose is Enz 500 mg qd, Gem 1250 mg/m 2 , and Cis 75 mg/m 2 . This regimen is generally well tolerated across all dose levels and there are no significant alterations in PK parameters of any drug, when given in combination. [Table: see text]
Effects of abiraterone acetate and enzalutamide on muscle and adipose mass in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Ecaterina Ileana, Sami Antoun, Laurence Albiges, Christophe Massard, Mario Di Palma, Bernard J. Escudier, Karim Fizazi, Yohann Loriot
Journal: Journal of Clinical Oncology (2013)

5088 Background: Abiraterone acetate (AA) and enzalutamide (MDV3100), two androgen receptor-directed compounds, have been shown to improve survival for patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after Docetaxel.. Since these drugs might be used at an early-stage in the future, and skeletal muscle (SM) and adipose tissue (AT) are known to be prognosis parameters, the aim of this study was to evaluate the body composition changes in patients with mCRPC treated with AA and MDV3100. Methods: Patients included in AFFIRM (n=62 treated with MDV3100 and placebo n=28) and COU-AA-301 (n=24 treated with AA+Prednisone (P)10mg/day and placebo+P n= 13) trials at the Institute Gustave Roussy were included in the analysis. Cross-sectional areas (cm 2 ) of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and SM were assessed by computed tomography imaging at 3 rd lumbar vertebra and were indexed for height (cm 2 /m 2 ) with Slice-O-Matic software V4.3 at baseline, 3, 6 and 12 months of treatment. The data from patients treated with AA or MDV3100 were compared to placebo-patients and tissues changes were compared to baseline. We used the validated sarcopenic definitions as SM index less than 52.4 (cm 2 /m 2 ). Results: For all cohort, median age was 69 years (range: 48-83), median weight was 79 kg (range: 47-150) and median BMI was 25.9 kg/m 2 (range: 18-46). At inclusion, 74 patients (58%) were overweight or obese (BMI&gt;24.9 kg/m2), and only 2 patients were underweight (BMI&lt;18.5kg/m2). 97 patients (81%) were sarcopenic, and 56 (75%) of overweight or obese patients were sarcopenic. Over 3 months, the patients from the entire cohort lost muscle mass (mean change: 4.5±7.5% (» 0.7 kg of muscle)) (P=0.01) . A non significant loss of SAT -4.6±19.2% and a non significant increase of VAT (+10.7±50.3% ) were observed. A similar pattern was observed at 6 months. There was no significant difference between body composition changes in treated groups and placebo. Conclusions: Sarcopenia is highly prevalent in patients with advanced CRPC. Unexpectedly, no difference in body composition changes was observed between patients treated with MDV3100 or AA and placebo.
Abstract 13297: Temporal Changes in Management of Heart Transplant Recipients and Impact on Coronary Allograft Vasculopathy
Authors: Kiyoko Uno, Randall C Starling, Amy Hsu, Craig Balog, Amar Krishnaswamy, Yu Kataoka, Rishi Puri, Kathy Wolski, Samir Kapadia, E Murat Tuzcu, Steven E Nissen, Stephen J Nicholls
Journal: Circulation (2012)

Background: The progression of coronary allograft vasculopathy (CAV) portends an adverse clinical outcome in heart transplant recipients. It is unknown whether temporal changes in the medical treat...
Reversible tumor metastases growth acceleration following bevacizumab interruption and surgical resection of metastases
Authors: T. Boisserie, W. Cacheux, O. Vignaux, B. Dousset, O. Soubrane, S. Chaussade, F. Goldwasser
Journal: Journal of Clinical Oncology (2007)

14119 Background: The addition of bevacizumab (BV), an anti-VEGF monoclonal antibody with antiangiogenic activity, to cytotoxic chemotherapy (CH) improves survival in metastatic colorectal cancer patients (pts). Reversal of VEGF inhibition is associated with rapid vascular regrowth in tumors in vivo (M.R. Mancuso et al, J Clin Invest; 116(10): 2610–2621, 2006). In the clinical setting, the consequences of BV interruption are poorly documented, especially in interactions with the surgical resection of liver metastases. Methods: We describe the kinetics of tumor growth prior to, during, and after interruption of BV and under BV reintroduction, in consecutive colorectal cancer pts experiencing objective response under CH+BV, followed by surgical resection of metastases. We measured either clinically, of using CT-scan, the diameter of target lesions according to RECIST criteria, and the doubling time. Results: 7 pts (3 F, 4M), with median age of 54 years (41–70), were treated with 5-FU based CH (+oxaliplatin: 5; + irinotecan: 1 pt) and BV for metastatic colo- (6 pts) rectal (1 pt) cancer received a median number of 6 (4–18) cycles. Median time between BV interruption and surgery: 8 weeks (3–12). Under BV, all pts experienced objective response, with a median tumor reduction of 13%/month (extr: 6–15%). After BV interruption, under CH alone, 2/7 pts experienced disease progression, with a tumor growth of the residual disease of +7% and +200%/month, respectively. In pts who underwent surgery, during the off therapy period, tumor growth occurred in all 7 pts with a kinetics of +17 to +400%/month. Tumor growth doubling time after BV interruption ranged between 2 and 5 weeks. Reintroduction of BV re-induced a tumor response in 5/7 pts with a median time to response of 8 weeks (6–12) and a reduction of 10%/month. Conclusions: We show reproducible evidence of tumor growth acceleration following BV interruption. Surgery might transiently modify the balance between angiogenic and anti-angiogenic factors. We suggest to reduce the duration of BV interruption and to restart BV as soon as possible after surgery. These observations justify a large prospective analysis of the variations of tumor growth in this setting. No significant financial relationships to disclose.
Defining mild, moderate, and severe fatigue in cancer patients and survivors: E2Z02, a trial of the Eastern Cooperative Oncology Group.
Authors: Xin Shelley Wang, Fengmin Zhao, Michael Fisch, Tito R. Mendoza, Ann M. O'Mara, David Cella, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2012)

9099 Background: Although mild, moderate and severe categories have been used in clinical guidelines for fatigue management in cancer patients, the optimal cutpoints on a 0-10 scale for delineating these categories have not been replicated. Methods: A multicenter ECOG study (E2Z02) enrolled breast, lung, prostate, or colorectal cancer patients with any treatment status. Fatigue and symptom interference were measured on the 0-10 numerical rating scale of the M. D. Anderson Symptom Inventory (MDASI). The optimal boundaries for categorizing fatigue severity were determined by the largest F ratios from MANOVA (Serlin’s criteria, 1995). Logistic regression with robust standard errors was used to identify risk factors for moderate/severe fatigue for cancer survivors (defined as patients with no evidence of disease and receiving no cancer treatment). Results: The optimal cutpoints that identified 3 distinct levels of fatigue severity for the 2341 patients were: ratings of 1-3 as mild, 4-6 as moderate, and 7-10 as severe. Known-group validity for these cutpoints was established by significant differences of fatigue severity by ECOG performance status and patient-reported quality of life (all P&lt;0.001). Using these cutpoints, 45% (983/2177) of patients undergoing active therapy had moderate/severe fatigue, with significant more mild fatigue in breast and colorectal cancer patients, while more severe fatigue in lung cancer patients (p&lt;.001). Among cancer survivors, 29% (150/515) had moderate/severe fatigue (breast 31%, colorectal 27%, prostate 22%, lung 33%). Younger age (OR=0.97, 95% CI=0.95-0.99) and poor performance status (OR=4.21, 95% CI=2.36-7.51) were associated with more moderate/severe fatigue in cancer survivors. Survivor time was also associated with moderate/severe fatigue in breast and colorectal cancer survivors (&gt;=5yrs vs. &lt;5yrs: OR=0.23, P&lt;0.01 for breast, OR=9.3, P=0.03 for colorectal). Conclusions: This multicenter study confirmed the standard cutpoints for fatigue severity used in NCCN fatigue management guidelines. It also provides a profile of moderate to severe fatigue prevalence for actively treated cancer patients and for cancer survivors.
Endoscopic submucosal dissection for remnant rectal neoplasm after ileal pouch-anal anastomosis for ulcerative colitis
Authors: Shunsuke Yoshii, Shinichiro Shinzaki, Yoshito Hayashi, Yoshiki Tsujii, Munehiro Ashida, Hideki Iijima, Tetsuo Takehara
Journal: Endoscopy (2019)

Restorative proctocolectomy with stapled ileal pouch-anal anastomosis (IPAA) has been a routinely performed surgical procedure for ulcerative colitis (UC); however, tumor development from the remnant rectal mucosa is problematic [1] [2]. Here, we report a case of successful endoscopic submucosal dissection (ESD) for a neoplasm arising from the remnant rectal mucosa after proctocolectomy for refractory UC ([Video 1]).
Complete disappearance of retroperitoneal lymph nodes after induction chemotherapy in advanced nonseminomatous germ cell tumors (NSGCT): Is there a place for adjunctive surgery?
Authors: Alexey Tryakin, Mikhail Fedyanin, Andrey Mitin, Urii Sergeev, Konstantin Figurin, Igor Fainstein, Tatiana Zakharova, Dheepak Kanagavel, Ljudmila Kostjakova, Dmitry Titov, Avgust Garin, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2012)

e15029 Background: The management of patients (pts) with a radiographic complete disappearance of retroperitoneal lymph nodes (CD-RPLN) metastases after chemotherapy (CT) remains controversial. Some authors recommend post-CT retroperitoneal lymph node dissection (PC-RPLND), whereas others omit surgery and observe these pts. In this retrospective study we analyzed outcome of pts with advanced NSGCT who achieved CD-RPLN and did not undergo PC-RPLND. Methods: From 1988 to 2008, 886 CT-naïve pts with advanced NSGCT were treated in our department with first-line cisplatin- and etoposide-based CT. All residual tumors &gt;1cm were resected when it was feasible. Pts who had CD-RPLN (≤1cm by CT-scan) and normalized tumor markers after CT were included into the study. Results: One hundred thirty seven pts were identified. 30% pts had teratoma in primary tumor. Following CT 13 pts underwent resection of extra-retroperitoneal lesions, no viable carcinoma was found. Good, intermediate and poor IGCCCG prognosis had 87 (64%), 33 (24%) and 17 (12%) pts, respectively. After a median f.-up of 72 (6-193) months, 11 (8%) pts relapsed. All but one relapses occurred in the first two years. Only 4 (3%) relapses developed in RPLN and were treated with salvage CT and surgery, all 4 pts died. Relapse rate in RPLN was equal among prognostic groups (good 2(2%), intermediate 1(3%), poor 1(6%) pts). 5-years OS were 94%, 97% and 79%, respectively. Conclusions: Pts obtaining complete disappearance of RPLN after induction CT had low risk of relapse and can be safely observed without surgery.