tbuckley/cabot-search huggingface dataset:
A phase II study of first-line erlotinib in patients (pts) with stage IIIB/IV non-small-cell lung cancer (NSCLC) including dose escalation to toxicity in current and former smokers (C/FS)
Authors: B. Besse, E. F. Smit, E. Felip, S. Siena, F. Blackhall, F. Barlesi, G. Giaccone
Journal: Journal of Clinical Oncology (2008)

8111 Background: Skin rash has been associated with increased activity of erlotinib in retrospective analyses and plasma levels of erlotinib are lower in current vs former or non-smokers (NS), potentially due to tobacco-induced enzyme activation. This parallel phase II study was initiated to determine the efficacy of erlotinib in chemonaïve pts with advanced NSCLC, at a fixed dose in NS, and a toxicity- driven dose in C/FS. The study is still accruing pts. Methods: Oral erlotinib (150mg/d) was given once daily to all pts; this was increased by 50mg increments to a maximum of 300mg/d in C/FS. Each dose was given for 2 wks; if no treatment-related toxicity (TRT) ≥ gr 3 occurred, the dose was escalated. The primary endpoint was non-progression rate (NPR) after 8 wks. Secondary endpoints included response, disease control rate (DCR; CR+PR+SD), safety, and correlative efficacy analyses. Results: Data are available for 41 pts: 21 NS and 20 C/FS. NS were more likely to be women than men (81% vs 19%, compared with 45% vs 55% in C/FS) and there were no cases of squamous-cell carcinoma among NS, compared with 2 cases in C/FS. Dose escalation was possible in the majority of C/FS (16/18 pts with data available), including 5 pts who were escalated to 300mg/d and a further 7 pts escalated to 250mg/d. NPR (n=34) was 59% in all pts after 8 wks; NPR was 50% for C/FS (n=16) and 67% for NS (n=18). Data on best response are available for 8 C/FS and 13 NS. 4 NS had partial responses (PR) and 8 had stable disease (SD) (DCR 92%). 3 C/FS had a PR (1 at 200mg/d, 1 at 250mg/d and 1 at 300mg/d) and 4 had SD (1 at 250mg/d and 3 at 300mg/d) (DCR 88%). In safety analyses (evaluable n=38), 20% of pts reported a gr 3/4 TRT. 28 pts reported rash (12 C/FS, 16 NS; no gr 3/4) and 18 pts reported diarrhea (8 C/FS, 10 NS; 1 gr 3). Conclusions: Erlotinib is a well-tolerated and effective treatment option in first-line NSCLC, with a NPR of ≥50% and a DCR of >85% in all evaluable pts. Increasing the dose of erlotinib in pts with a history of smoking can potentially increase the activity of this agent in these pts. Pharmacokinetic and predictive biomarker analyses will be carried out. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Roche
Impact of physician visits on bone density testing in men with prostate cancer who receive androgen deprivation therapy.
Authors: Candice Yong, Ebere Onukwugha
Journal: Journal of Clinical Oncology (2014)

291 Background: Clinical guidelines for men receiving androgen deprivation therapy (ADT) for prostate cancer (PC) recommend bone mineral density (BMD) monitoring. We examined physician visit patterns following ADT initiation and the implications for follow up BMD testing. Methods: We analyzed linked Surveillance, Epidemiology, and End Results (SEER) &amp; Medicare data for men aged 65+ with incident non-metastatic PC diagnosed during 2007-2009 and receiving ADT for at least 6 months. We examined the proportion of men who visited the following physician types after ADT initiation: urologist, medical oncologist (MO), radiation oncologist (RO), and primary care physician (PCP). Physician contact was measured during 3 time periods: 3 months pre-ADT and 3 months post-ADT (P1); 3-6 months post-ADT (P2); and 6-9 months post-ADT (P3). Multivariable logistic regression models estimated the association between physician visits and BMD testing. Results: The sample included 4,631 men (median age: 75) with non-metastatic PC who received ADT over a median duration of 12 months. During follow-up, 12% received BMD testing, and median time from ADT initiation to BMD testing was 364 days. The proportion who visited any urologist, MO, RO, and PCP during P1 was 97%, 12%, 52%, and 71%. During P2, the proportions dropped to 69%, 9%, 19%, and 53%, respectively, and remained similar in P3. Physician visits during P1 were not associated with BMD testing. During P2, the adjusted odds ratio (95% CI) for BMD testing in men who saw a MO was 1.39 (1.04-1.86). During P3, the AOR (95% CI) was 1.52 (1.15-2.01) in men who saw a MO and 1.23 (1.02-1.49) in men who saw a PCP. Conclusions: In older PC men treated with ADT, physician contact was highest during ADT initiation and decreased over time. Continued contact with physicians following ADT initiation can be beneficial.
Phase I/ II study of genasense (G3139) in combination with cisplatin (Cis) and fluorouracil (FU) in patients with advanced esophageal, gastro- esophageal junction and gastric cancer (P5385)
Authors: A. Kaubisch, Y.-H. Wu, S. Wadler
Journal: Journal of Clinical Oncology (2005)

9695 Background G3139 is an 18-mer anti- Bcl-2 phosphorothioate oligonucleotide. In vitro G3139 enhances chemotherpy- induced apoptosis. In a gastric cancer xenotransplant model the combination of G3139 with cisplatin enhanced response and survival. (J Mol Med, 2001. 79(10): p. 587–93). Methods Patients (pts) with pathologically confirmed, inoperable, locally advanced or metastatic adenocarcinoma of the stomach or GE-junction, or squamous cell carcinoma of the esophagus were eligible. One course of prior chemotherapy treatment was allowed. G3139 was started at 3 mg/kg/d x 7d continuous infusion (ci); Cis was initially given at 100 mg/m2 on d1, FU was given at 1000 mg/m2/d as ci on days 4–8. Cycles were repeated every 21 days. Results 13 pts (mean age 52, 37–64) have been enrolled in the phase I portion of the study, 11 pts have been treated for an average of 3.2 cycles (1–7). 2 pts became ineligible between enrollment and planned treatment. At the initial dose level mucositis was common and resulted in a DLT. The doses of FU (750 mg/m2/d x 4d) and Cis (75 mg/m2 on D1) were lowered, and the FU infusion was shortened to 4 days. G3139 was then escalated to 5mg/kg/d without further DLT’s. Accrual continues; 3 pts so far had serial tumor biopsies for microarray analysis. Nine pts are evaluable for response. There has been one CR, two PRs, three SDs and three PDs. The responding patients have chosen to discontinue therapy after 7,4, and 7 cycles respectively. Two were feeling well, one was bothered by grade 2 fatigue. The pt with the CR remains free of disease at 14 months. Conclusions Grade 2 anemia is the most common side effect noted to date on this study. So far it is unclear to what degree the Bcl-2 antisense oligo G3139 contributes to the responses noted to date. No significant financial relationships to disclose.
Ethnicity and excess mortality in severe mental illness: a cohort study
Authors: Jayati Das-Munshi, Chin-Kuo Chang, Rina Dutta, Craig Morgan, James Nazroo, Robert Stewart, Martin J Prince
Journal: The Lancet Psychiatry (2017)

Excess mortality in severe mental illness (defined here as schizophrenia, schizoaffective disorders, and bipolar affective disorders) is well described, but little is known about this inequality in ethnic minorities. We aimed to estimate excess mortality for people with severe mental illness for five ethnic groups (white British, black Caribbean, black African, south Asian, and Irish) and to assess the association of ethnicity with mortality risk.We conducted a longitudinal cohort study of individuals with a valid diagnosis of severe mental illness between Jan 1, 2007, and Dec 31, 2014, from the case registry of the South London and Maudsley Trust (London, UK). We linked mortality data from the UK Office for National Statistics for the general population in England and Wales to our cohort, and determined all-cause and cause-specific mortality by ethnicity, standardised by age and sex to this population in 2011. We used Cox proportional hazards regression to estimate hazard ratios and a modified Cox regression, taking into account competing risks to derive sub-hazard ratios, for the association of ethnicity with all-cause and cause-specific mortality.We identified 18 201 individuals with a valid diagnosis of severe mental illness (median follow-up 6·36 years, IQR 3·26-9·92), of whom 1767 died. Compared with the general population, age-and-sex-standardised mortality ratios (SMRs) in people with severe mental illness were increased for a range of causes, including suicides (7·65, 95% CI 6·43-9·04), non-suicide unnatural causes (4·01, 3·34-4·78), respiratory disease (3·38, 3·04-3·74), cardiovascular disease (2·65, 2·45-2·86), and cancers (1·45, 1·32-1·60). SMRs were broadly similar in different ethnic groups with severe mental illness, although the south Asian group had a reduced SMR for cancer mortality (0·49, 0·21-0·96). Within the cohort with severe mental illness, hazard ratios for all-cause mortality and sub-hazard ratios for natural-cause and unnatural-cause mortality were lower in most ethnic minority groups relative to the white British group.People with severe mental illness have excess mortality relative to the general population irrespective of ethnicity. Among those with severe mental illness, some ethnic minorities have lower mortality than the white British group, for which the reasons deserve further investigation.UK Health Foundation and UK Academy of Medical Sciences.
Radiation oncology whiteboard: Data and workflow manager for enhanced communication and task management.
Authors: John A. Wolfgang, Theodore S. Hong
Journal: Journal of Clinical Oncology (2012)

304 Background: Patient care within the radiation oncology clinic consists of several interdependent data driven procedures which must be executed in concert to ensure the best possible patient care. State of the art treatment in radiation oncology is largely computer driven, where patient care relies on the use of a typically vendor dependent, heterogeneous server environment. Traditional, peer-to-peer communication in such an environment introduces a fault intolerant workflow, where failed communication and data inconsistency issues may result in delayed or inappropriate patient treatment. Methods: The MGH Radiation Oncology Whiteboard is an intranet based application allowing for live monitoring of these patient care tasks available across the entire radiation oncology clinical domain. Patient events are recorded through interaction from various care-givers and data sources within the department, changing state as well as collecting event data from the accomplished task. Personnel may be alerted of state changes through automatic, customizable paging, email and live monitoring notification, triggering subsequent steps in the workflow chain. Currently the Whiteboard leverages data from multiple points in the clinic including: CT Simulation and data (4D), treatment planning written directive, dvh plan results, imrt and sbrt plan QA, daily and monthly linac QA, IORT coordination and calculation check, linear accelerator engineering log, patient treatment wait time (linac), remote treatment plan review. Results: Since introduction of the Whiteboard into the MGH clinic in 2008, task compliance in key areas, such as contour definition, radiation dose prescription, imrt QA measurement completion and pre-treatment plan checking has risen to levels well above 95%. Conclusions: Monitoring of patient care events improves QA by eliminating peer-to-peer communication and introducing complete transparency to the workflow communication chain. This approach enables all members of the staff to become active participants in the quality control process, every individual, through interaction with the Whiteboard, acting as an additional QC filter to improve patient care.
Do we need daily corticosteroid combined with docetaxel when treating against castration-resistant prostate cancer?
Authors: Tatsuya Shimomura
Journal: Journal of Clinical Oncology (2016)

184 Background: Depend on the result of TAX 327, docetaxel are usually used with daily corticosteroid (prednisone) against castration resistant prostate cancer (CRPC). However there is no evidence that combination of daily corticosteroid itself with docetaxel improve survival rate. In this study we investigated whether daily corticosteroid have survival benefit in our docetaxel treatment cohort. Methods: Total of 120 CRPC cases were treated with docetaxel in our department between 2011 and 2014. We compared the group 1 (with daily corticosteroid) and group 2 (without daily corticosteroid) and evaluated their clinical outcome. In group 2, there was no case using estramustine or any estrogen medicine. Results: Group 1 was 104 cases and group 2 was 11 cases in this study. In terms of clinical and pathological demographics at diagnosis of prostate cancer and at starting docetaxel, almost all of the factors did not have significant difference between group1 and 2 other than white blood cell count(mean 7142 and 5664, respectively. p = 0.0449). About the treatment outcome, there were no significant difference in overall survival (p = 0.8696) , PSA response rate (39.2% vs 52.0%, p = 0.2348), PSA decline ³a50% (38.4% vs 45.5%,p = 0.651), PSA decline ³a90% (14.4% vs 36.4%, p = 0.062) and number of cycles (Mean 7.19 vs 8.33, p = 0.174) between group 1 and 2. Conclusions: Although this study was retrospective and the cohort was small, we did not find the difference of outcome among the 2 groups. At least, we could say that there was no survival benefit in the daily corticosteroid groups. And there is a possibility that we do not need to combine daily corticosteroid with docetaxel. We will need prospective randomized trial to prove this hypothesis.
Is neoadjuvant therapy beneficial in clinically staged T2N0 esophageal cancer?
Authors: Taranjeet Kaur, James P. Dolan, Brian S. Diggs, Renato Luna, Brett C. Sheppard, Paul Schipper, Brandon Tieu, John M. Holland, Charles R. Thomas, Ken Gatter, Gina M. Vaccaro, John G. Hunter
Journal: Journal of Clinical Oncology (2013)

135 Background: The optimal treatment strategy for clinical stage T2N0 (cT2N0) esophageal cancer is poorly defined. The specific aims of this analysis were to determine the impact of neoadjuvant therapy (NAT) in cT2N0 esophageal cancer patients on overall survival, nodal metastasis, staging, and pathological complete responders (pCR) NAT. Methods: We reviewed a retrospective cohort of 27 patients with cT2N0 esophageal cancer at Oregon Health &amp; Science University, an NCI-Designated Cancer Center from 1999 to 2011. All patients were staged pre-operatively using Endoscopic Ultrasound (EUS), CT +/- FDG-PET. Patients were identified into two cohorts: NAT followed by surgery and surgery alone. We compared overall survival between the cohorts using Kaplan-Meier analysis. Results: Eleven patients (41%) received NAT followed by surgery and sixteen patients (59%) underwent surgery alone. Minimal invasive esophagectomy and decreased length of stay (p &lt; 0.05) were associated with the presence of neoadjuvant therapy. The difference in overall survival rate was not statistically significant between NAT and surgery alone groups (p = 0.96). Three of 11 patients (27%) had a pCR and 8 (73%) were partial or non responders after NAT. In the surgery only group, nine of 16 patients (56%) were understaged, 6 (38%) were overstaged and 1 (6%) was correctly staged. Despite being clinically node negative, 14/27 (52%) had node positive disease in both groups with 5/11 (45%) in NAT group and 9/16 (56%) in surgery group. Conclusions: The benefit of NAT in cT2N0 esophageal cancer patients remains unclear. However, our finding of significant clinical understaging and frequent positive nodes in clinically node negative patients suggests a clinical benefit to NAT for some cT2N0 patients before surgery. These observations support design of a prospective clinical trial to define the role of NAT in patients with cT2N0 esophageal cancer.
Outcome of patients with advanced non-transitional urothelial carcinomas following platinum-based chemotherapy
Authors: E. Kastritis, G. Bozas, E. Efstathiou, V. Koutsoukou, D. Gika, C. Deliveliotis, N. Antoniou, M. A. Dimopoulos, A. Bamias
Journal: Journal of Clinical Oncology (2005)

4596 Background: Non-transitional carcinomas account for less than 5% of all malignant neoplasms of the bladder and upper urinary tract in Europe and USA. There have been reports suggesting a worse outcome of non-transitional carcinomas following cystectomy, but there is limited information regarding the benefit from systemic chemotherapy in this population. We, therefore, analysed the efficacy of platinum-based chemotherapy in patients with pure squamous or mixed carcinomas who had been entered into our database and we compared it with that in pure transitional carcinomas. Methods: 404 consecutive patients with advanced cancer were included in this analysis. All patients had been treated with cisplatin or carboplatin-based chemotherapy within the context of 5 studies. 25 patients (6.2%) had mixed histology (transitional + squamous: 24, transitional + sarcomatoid: 1) and 17 patients (4.2%) had pure squamous carcinoma. Results: There were no statistically significant differences in baseline characteristics (sex, PS, haemoglobin, weight loss, sites of metastases), although there was a trend for more frequent distant metastases in non-pure transitional carcinomas (mixed 60%, squamous 70%, pure transitional 48%, p=0,122). Median follow up of living patients was 39.2 months. Objective response rates did not differ significantly according to histology (mixed 32%, squamous 35%, pure transitional 44%, p=0,381). Median survival of mixed carcinomas was 9 months, squamous carcinomas 16.6 months and pure transitional 11 months (p=0.386).Univariate analysis of baseline characteristics showed that ECOG PS 2 or 3 and hemoglobin < 10 were associated with worse prognosis in mixed histology (p<0.0001 and p=0.005), while hemoglobin < 10 was also an adverse prognostic factor in squamous carcinomas (p=0.09). Conclusions: Non-transitional histology does not predict for an inferior outcome after platinum-based chemotherapy for advanced urothelial carcinoma. Well known prognostic factors in transitional cell carcinomas (PS and baseline haemoglobin) were also associated with prognosis in mixed and squamous cell carcinomas. No significant financial relationships to disclose.
EGFR FASTnet: The Italian network for epidermal growth factor receptors (EGFR) mutation analysis in non-small cell lung cancer (NSCLC).
Authors: N. Normanno, C. Pinto, G. L. Taddei, E. Mari, G. Troncone, P. Graziano, M. Mottolese, V. Ludovini, S. Zupo, G. De Maglio, A. Russo, L. M. Larocca, M. Di Maio, M. Gambacorta, O. Nappi, G. Viale, A. Ardizzoni, L. Crinò, F. Perrone, A. Marchetti
Journal: Journal of Clinical Oncology (2011)

e18026 Background: Gefitinib was approved in Italy for treatment of NSCLC pts carrying mutant EGFR in May 2010. Methods: The EGFR FASTnet program was designed to facilitate the exchange of biological material, clinico-pathological data and diagnostic reports between medical oncologists, primary pathologists and referral laboratories through a dedicated website (www.egfrfastnet.it), a call center and a courier. EGFR mutational analysis was carried by Sanger sequencing, Real Time PCR, Pyrosequencing, Fragment Analysis and High resolution melting (HRM). The Italian Association of Medical Oncology (AIOM) and the Italian Society of Surgical Pathology and Cytopathology (SIAPEC-IAP) have full access to the anonymous database of EGFR FASTnet. Results: The EGFR FASTnet network started in July 2010 and as of January 2011, 272 oncologists, 75 primary pathologists and 12 referral laboratories joined the program. In this period 658 pts were enrolled. The cohort of pts was significantly enriched for adenocarcinoma histology (73.4%), female sex (37.5%) and smoking history (never smoker 25.7%, former smoker>15 yrs 21.4%, light smoker 6.1%). Mutational analysis was feasible in 593 pts (90.1%), on the primary tumor (444, 74.8%) or metastases (149, 25.2%). At the registration, 54,4% of the pts had not received yet treatment for advanced disease. Mutational analysis was carried by Sanger sequencing in 67% of the pts. EGFR mutations were found in 84 cases (14.2%), mainly in exons 19 (69%) and 21 (29.8%). A higher mutation rate was found in never smokers (28.6%), former smokers >15 yrs (15.2%) and light smokers (16.7%), as well as in adenocarcinoma/BAC (15.4%) and females (23.2%). Conclusions: The EGFR FASTnet network allows assessment of EGFR mutations in a population of Italian NSCLC pts in centers with or without molecular biology facilities. The pts to be tested for EGFR mutations are spontaneously selected by medical oncologists according to known predictive factors. The results of the mutational analysis from clinical practice are consistent with data from literature. This program is supported by AstraZeneca Italy.
Quality of life and depression during hospitalization for hematopoietic stem cell transplantation to predict quality of life and post-traumatic stress disorder symptoms at 6 months post-transplant.
Authors: Areej El-Jawahri, Harry VanDusen, Lara Traeger, Joel Fishbein, Tanya Keenan, Joseph A. Greer, William F. Pirl, Vicki A. Jackson, Justin Eusebio, Emily R. Gallagher, Thomas R. Spitzer, Karen K. Ballen, Steven L. McAfee, Bimalangshu Dey, Yi-Bin Albert Chen, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2015)

215 Background: Patients undergoinghematopoietic stem cell transplantation (HCT) experience a steep deterioration in quality of life (QOL) and mood during hospitalization for HCT. The impact of this deterioration on patients’ long-term QOL and post-traumatic stress disorder (PTSD) symptoms is unknown. Methods: We conducted a prospective longitudinal study of patients hospitalized for HCT. At baseline (day-6), day+1, day+8, and 6 months post-HCT, we assessed QOL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation [FACT-BMT]) and mood (Hospital Anxiety and Depression Scale [HADS]). We used the PTSD Checklist to assess for PTSD symptoms at 6 months. We used multivariable linear regression models to identify predictors of QOL and PTSD symptoms at 6 months post-HCT. Results: We enrolled 97% (90/93) of consecutively eligible patients undergoing autologous (n = 30), myeloablative allogeneic (n = 30), or reduced intensity allogeneic (n = 30) HCT. Overall, patients’ QOL at 6 months (mean FACT-BMT: 110, 95%CI [104-116]) recovered to baseline pre-transplant values (mean FACT-BMT: 110, 95% CI [107-115]). At 6 months, 28.4% of participants met provisional diagnostic criteria for PTSD, and 43.3% had clinically significant depression. In multivariable regression analyses adjusting for baseline QOL, mood, other covariates, change in QOL and depression scores during hospitalization for HCT predicted impaired QOL (DQOL β = 1.13, P &lt; 0.0001, D HADS-depression β = 2.51, P = 0.001) and PTSD symptoms (DQOL β = 0.50, P &lt; 0.0001, DHADS-depression β = 1.22, P &lt; 0.0001) at 6 months post-HCT. Conclusions: While patients’ overall QOL at 6 months post-HCT returned to baseline values, a significant proportion met provisional diagnostic criteria for PTSD and depression. The decline in QOL and increase in depressive symptoms during hospitalization for HCT were the most important predictors of long-term QOL impairment and PTSD symptoms. Future studies should evaluate whether interventions to improve QOL and reduce psychological distress during HCT may improve long-term QOL and reduce the risk of PTSD symptoms.