tbuckley/cabot-search huggingface dataset:
Loss of Two Steroid 11β-Hydroxylating Components in a Rat Adrenocortical Carcinoma2
Authors: Max L. Sweat, Melvin J. Bryson
Journal: JNCI Journal of the National Cancer Institute (1964)

Examination of the Snell homologously transferred rat Adrenocarcinoma 494 indicated a loss of two components (F-40 and F-80) associated with steroid 11β-hydroxylation in normal adrenal tissue. The tumor retained the mechanisms associated with 21-hydroxylation of progesterone and C-5 isomerization and C-3 oxidation of pregnenolone.
Circulating angiogenic factors as predictors of benefit from bevacizumab (bev) beyond progression in metastatic colorectal cancer (mCRC): Traslational analyses from the phase III BEBYP trial.
Authors: Carlotta Antoniotti, Fotios Loupakis, Chiara Cremolini, Guido Bocci, Anna Fioravanti, Gianluca Masi, Lisa Salvatore, Federica Marmorino, Paola Orlandi, Marta Schirripa, Francesca Bergamo, Federica Zoratto, Teresa Di Desidero, Bastianina Canu, Romano Danesi, Alfredo Falcone
Journal: Journal of Clinical Oncology (2013)

3603 Background: TML and BEBYP trials demonstrated that the strategy of prosecuting bev beyond progression is effective in mCRC. Previous analyses from phase II studies showed that a modulation of plasma angiogenic factors occurs during 1 st -line treatment with chemotherapy (CT) + bev and a wide variability in soluble Vascular Endothelial Growth Factor Receptor-2 (sVEGFR-2) levels was observed at the time of progression. Moving from preliminary analyses in murine models we selected a pool of candidate ligands to be tested in the clinical setting. Methods: sVEGFR2, Placental Growth Factor (PlGF), Platelet-Derived Growth Factor-C, basic Fibroblast Growth Factor, Angiopoietin-2 and soluble Tie-2 were assessed by ELISA on plasma samples collected at baseline in a cohort of 59 patients enrolled in phase III BEBYP trial of 2nd-line CT ± bev beyond progression to a bev-containing first-line regimen. Plasma levels were defined high or low adopting the median values as cut-off. Results: A significant interaction between treatment arm and baseline sVEGFR-2 levels was observed (p=0.036). Among 30 patients with high sVEGFR-2 levels, the prosecution of bev was associated with a significant benefit in terms of PFS (median: 10.4 vs 3.4 months, HR 0.37 [95%CI 0.10-0.58], p=0.0015), that was not evident among 29 patients with low sVEGFR-2 levels (5.4 vs 5.0 months, HR 0.98 [95%CI 0.45-2.11], p=0.956). Despite a trend towards a greater benefit from bev among 30 patients with high PlGF levels (HR 0.45 [95%CI 0.13-0.86]), no interaction between treatment arm and baseline PlGF levels was observed (p=0.210). Combined analysis of sVEGFR-2 and PlGF showed that prosecuting bev provided a substantial benefit in PFS in the subgroup with high levels of both ligands (10.5 vs 2.3 months, HR 0.25 [95%CI 0.01-0.45], p=0.043). Conclusions: sVEGFR-2 levels at the time of first progression may predict benefit from prosecuting bev. Interesting results from simultaneous analysis of sVEGFR-2 and PlGF may be affected by a pronounced subgrouping and should be considered cautiously. Given their potential clinical value, these data need prospective confirmation. Clinical trial information: NCT00720512.
Correlation between c-erb-B2 overexpression with disease-free survival and rate of pelvic relapse in patients with advanced cervical cancer treated with chemo-radiotherapy
Authors: J. Pérez-Regadera, A. Sánchez-Muñoz, J. De-la-Cruz, C. Ballestín, D. Lora, R. García-Martín, L. Alonso-Carrión, C. Mendiola, E. Lanzós
Journal: Journal of Clinical Oncology (2007)

16004 Aims: To determine the impact of the c-erb-B2 overexpression receptor on pelvic relapse and on disease-free survival (DFS) in patients with advanced cervical cancer receiving concurrent chemo-radiotherapy. Methods: One hundred thirty six patients with advanced cervical cancer (stage: 12 IB2-IIA, 34 IIB, 71 IIIB, 19 IVA); histology: 86 epidermoid and 14 adenocarcinoma) were analyzed to detect c-erbB-2 level using an immunohistochemical method (Herceptest Dako). Cases c-erbB-2 (+3) were considered positive. All patients received pelvic radiotherapy, brachitherapy and concurrent chemotherapy with two schedules: 48 patients with tegafur (800 mg/day via oral) and 88 with tegafur (same doses) plus five cycles of weekly cisplatin 40 mg/m2/week iv. Results: Of the 136 biopsies, 32 (23.5%) were c- erbB-2 positive. The disease free survival to 3 and 5 years of the patients were 61% and 58% for c-erb-B2 negative and 36% and 36% for c-erb- B2 positive (p=0.02), respectively.We divided our patients in four groups: c-erb-B2 positive treated with cisplatin; c-erb-B2 positive without cisplatin, c-erb-b2 negative treated with cisplatin and c-erb-b2 negative without cisplatin. The group of patients with c-erb-B2 overexpression that did not received platinum treatment had a higher rate of pelvis relapse (p&lt;0.0001) and with a decreased DFS (p=0.0014). Conclusions: c-erbB-2 overexpression may imply a poor prognosis for patients with advanced cervix cancer, especially if they did not receive concurrent radiochemotherapy with cisplatin. No significant financial relationships to disclose.
Long-term results of MR-guided laser ablation (LITT) of liver metastases of breast cancer
Authors: M. G. Mack, K. Eichler, S. Zangos, T. Lehnert, T. J. Vogl
Journal: Journal of Clinical Oncology (2008)

1037 Background: Percutaneous LITT has received increasing attention for the treatment of a variety of primary and secondary malignant liver tumors. Surgical resection of liver metastases from breast cancer is still a subject of discussion. Systemic chemotherapy and/or hormone therapy are still considered the mainstay in the treatment of these patients. Nevertheless, although these therapies achieved response in 40–70% of cases, survival of patients with breast cancer liver mets is limited. The purpose of this study was to analyze the long term results of LITT for the treatment of liver metastases of breast cancer. Methods: 965 metastases in 421 consecutive patients (mean 55.7 years, range 23–84 years) were treated in 813 treatment sessions between 1993 and 2007. 6.0% of the patients had recurrent metastases after surgery, 45.8% metastases in both liver lobes, 27.7% refused surgical resection, 1.9% had contraindications for surgery and 18.9% had metastases at difficult localization for surgery. 73.4 patients were treated in curative intention (≤5 mets, no extrahepatic disease except controlled bone mets), 26.6 patients were treated in palliative intention (>5 mets and/or extrahepatic disease). All treatments were performed under local anesthesia, mainly on an outpatient basis. SRs were calculated using Kaplan-Meier method. Results: The mean overall SR was 4.6 years (95%CI 4.2–5.0 years, 1-year-SR 95%, 2-year-SR 77%, 3-year-SR 58%, 5-year-SR 35%) after diagnosis of treated metastases. In the curative patient-group the mean SR was 5.0 years (95% confidence interval: 4.5–5.4 years) and significantly superior to the palliative group with a mean survival of 3.2 years (95%CI: 2.7–3.7 years). Patients with 1 or 2 liver mets had superior SR (mean 5.1 years) versus patients with 2–4 or 5 and more liver mets (4.3 years and 3.4 years, respectively). The mean survival after the diagnosis of the first metastases was 6.2 years in the curative group and 6.0 years in the palliative group. The rate of clinical relevant complications was 1.4%. No death occurred. Conclusions: LITT is a safe and effective treatment option for patients with breast cancer liver metastases and should be included into the complete management of patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Somatex
Sex Differences in Fluorouracil-Induced Stomatitis
Authors: Jeff A. Sloan, Charles L. Loprinzi, Paul J. Novotny, Scott Okuno, Suresh Nair, Debra L. Barton
Journal: Journal of Clinical Oncology (2000)

PURPOSE: A meta-analysis of six North Central Cancer Treatment Group (NCCTG) trials involving patients receiving their first ever fluorouracil (5-FU)–based chemotherapy was undertaken to explore the association of sex with reports of the incidence and severity of stomatitis. PATIENTS AND METHODS: Data were obtained on a total of 731 patients (402 men and 329 women). Comparisons of incidence and severity rates and average stomatitis across sex were performed using standard binomial testing and t tests, respectively. Logistic regression analysis and a weighted analysis using data summarized to study level served as evidence of cross-validation. RESULTS: Women reported stomatitis both more often and with greater severity than did men. The incidence of any stomatitis for women was 63% versus 52% for men (P = .002). The incidence of severe or very severe stomatitis for men and women was 22% and 12%, respectively (P = .0006). On average, women reported stomatitis of roughly 0.4 points higher than men on a 0 to 4 ordinal scale (P &lt; .00001). Comparison of results across treatment and placebo arms was carried out to validate the initial findings. Logistic regression modelling further confirmed the results conditional on the presence of a number of potentially confounding covariates. Women were also 11% more likely than men to experience leukopenia of common toxicity criteria grade ≥ 1, (70% v 59%, respectively; P &lt; .00001) and grade 3+ (18% v 11%, respectively; P = .004). CONCLUSION: More women than men reported 5-FU–induced stomatitis. The precise mechanism resulting in different degrees of stomatitis across sex is not evident.
FEV1 is not a prognostic marker in operated patients with stage I or II non-small cell lung cancer (NSCLC)
Authors: Anouschka Cogen, Yanina Dockx, Annelies Janssens, Joost Weyler, Paul Van Schil
Journal: European Respiratory Journal (2011)

Background:  In retrospective studies lung cancer mortality was found to be higher in patients with chronic obstructive pulmonary disease (COPD), defined as a FEV 1  ≤70% of the predictive value. In the Cher@Nostrial and the Paccora trials, based on patients with unresectable clinical stage III, a strong relationship was observed between FEV 1  and overall survival (OS). In a smaller study FEV 1  was a prognostic factor for OS in operated patients (Nakaljima et al.Thor Cardiov Surg 2009;57:339-342).  In our study we investigated whether the presence of COPD is a prognostic marker in patients with resectable stage I and II NSCLC.   Methods:  All relevant clinical information was gathered retrospectively from 77 patients undergoing complete resection without preoperative chemo- or radiotherapy between January 2003 and January 2006.  All patients were staged according to the 7th TNM-classification.  Primary endpoints were OS and progression-free survival (PFS).  Follow-up information was complete for all patients and ended in July 2010.  Patients were classified as having a FEV 1  ≤70% or a FEV 1  >70%.   Results:  According to the Kaplan Meier analysis (log rank test) FEV 1  was not a significant prognostic factor for OS [p=0.461] or PFS [p=0.530]. In a Cox multiple regression analysis the adjusted hazard ratio for FEV 1 (measured on a continuous scale) was 1.632 (p=0.458) after adjustment for stage and age.   Conclusion:  In contrast to other studies our data show that FEV 1  is not a prognostic factor in patients with resectable stage I and II NSCLC. Precise selection criteria regarding cardiopulmonary function excluding patients with a very poor cardiopulmonary function, could be responsible for this finding.
Neoadjuvant chemotherapy with a dose-dense sequential combination of epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine ± trastuzumab in stage II and III breast cancer. Correlation between pathologic complete response (pCR) and biologic markers
Authors: A. Sanchez, R. Dueñas-García, A. Jaén-Morago, I. Chacón, A. García-Tapiador, E. Martínez-Ortega, C. de la Torre-Cabrera, B. Dueñas, N. Ribelles, P. Sánchez-Rovira
Journal: Journal of Clinical Oncology (2007)

595 Background: To evaluate the efficacy, measured as pCR, and safety of a noncross-resistant sequential and dose- dense schedule as neoadjuvant treatment for early breast cancer patients (pts). To correlate pCR with gene expression. Methods: Histologically confirmed stage II-III breast cancer pts, including inflammatory tumors, were treated first with epirubicin and cyclophosphamide (90/600 mg/m 2 ) for 3 cycles and then with paclitaxel and gemcitabine (150/2,500 mg/m 2 ) for 6 cycles. All drugs were administered on day 1, every 2 weeks with growth factor support. Weekly trastuzumab (2 mg/kg with a loading dose 4 mg/kg) was given concomitantly with paclitaxel and gemcitabine in Her2 positive pts. A biopsy was performed before treatment for the gene expression study. Pts underwent surgery, radiotherapy and adjuvant hormonal therapy according to institutional practice. Results: 73 pts with a median age of 45.3 (range 28.6–73.6) were enrolled; 42 (57.5%) T2, 12 (16.5%) T3 and 19 (26%) T4 (13 inflammatory). Median tumor size was 4 cm (1–10). 30 pts (41.1%) were hormonal receptor negative, 32 (43.8%) ki-67 positive, 10 (13.7%) p53 positive, 31 (42.5%) GIII and 20 (27.3%) Her2 positive. All pts responded; 27 (36.9%) achieved a pCR (absence of invasive tumor in the breast); 32.1% in Her2 negative pts and 50% in Her2 positive pts. 47 pts (64,4%) underwent conservative surgery. G3/4 hematologic toxicities were leukopenia in 6 pts (9%), neutropenia in 8 pts (12%) and anemia in 1 (2%). Most frequent G3/4 nonhematologic toxicities were nausea (13%) and vomiting (15%). Asymptomatic decrease in cardiac ejection fraction was observed in 1 pt treated with trastuzumab with subsequent normalization. Conclusions: These results show a highly effective regimen in terms of pCR with a good toxicity profile. The addition of trastuzumab increased the pCR rate in Her2 positive pts. Updated results, including correlation between pCR and biological markers and disease-free survival will be presented at the meeting. No significant financial relationships to disclose.
Dying for palliative care
Authors: J J McMullan
Journal: BMJ (1995)

Dying for palliatve care General practitioners have a crucial role EDrTOR,-The anonymous diary of a surgeon's death arouses compassion but also suggests that the general practitioner, who has a crucial role in palliative care, played a small part.'The general practitioner made a referral to hospital in August 1993 but seems to have had no part in the first two admissions, the decision to go to South Africa, or the subsequent hospital based treatment in March 1994 after the diagnosis of leukaemia.Serious difficulties in communication and considerable distress are described, but all we are told is that, three days after discharge from hospital, on 12 July, "Our GP called: asked for the third time
Comparison between neoadjuvant chemotherapy followed by surgery (NAC-S) and definitive chemoradiotherapy (CRT) in overall survival for patients with clinical stage II-III esophageal squamous cell carcinoma (ESCC) (JCOG1406-A).
Authors: Motoo Nomura, Ken Kato, Junki Mizusawa, Kozo Kataoka, Nobutoshi Ando, Kei Muro, Atsushi Ohtsu, Hiroyasu Igaki, Masayuki Shinoda, Hiroya Takeuchi, Hideaki Shimizu, Kazuhiko Hayashi, Hiroyuki Daiko, Masahiro Goto, Yoshito Komatsu, Kazuo Konishi, Yoshinori Miyata, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2015)

127 Background: NAC-S is a standard treatment for patients (pts) with stage II/III (UICC-TNM 5th ed.) ESCC in Japan. CRT is also optionally performed for pts who refused or who are not tolerable to surgery. However, no randomized clinical trial has been conducted comparing NAC-S with CRT. The aim of this study is to explore subgroups in which survival outcome of pts undergoing CRT was potentially equivalent to NAC-S. Methods: The data of two trials for cStage II/III ESCC, JCOG9907 (accrual period: 2000-2006) and JCOG9906 (2000-2002) were used. J9907 demonstrated that NAC-S (2 course of cisplatin and 5-fluorouracil [CF] followed by surgery) showed superior OS compared with surgery followed by postoperative chemotherapy. J9906 was a single arm trial which explored the efficacy and safety of CRT (CF plus 60 Gy). Both two trials were conducted under similar eligible criteria. Subgroup analyses between two trials (serum Albmin (Alb), cT, cN, c-stage, and tumor location) using Cox proportional hazard model were performed for pts assigned to receive NAC-S in J9907 and pts in J9906. Results: All eligible pts for NAC-S group (n=164) in J9907 and all eligible pts in J9906 (CRT group: n=73) were analyzed. Pts backgrounds were similar between two groups. OS for NAC-S group was better than that for CRT group (adjusted HR 1.73; 95% CI 1.19-2.51). Subgroup analysis using Cox proportional hazard model demonstrated that all subgroups in NAC-S group showed shorter OS compared with those in CRT group (see Table). Conclusions: OS of NAC-S was favored over that of CRT. The subgroup in which OS of CRT was equivalent to that of NAC-S was not detected. For further improvement of CRT for this population, single arm trial (JCOG0909) is ongoing to evaluate the efficacy and safety of CRT modifying chemotherapy regimen and total radiation dose. [Table: see text]
A phase II study of erlotinib in combination with capecitabine in previously treated patients with metastatic pancreatic cancer
Authors: L. S. Blaszkowsky, K. H. Kulke, D. P. Ryan, J. W. Clark, J. Meyerhardt, A. X. Zhu, C. Lawrence, C. S. Fuchs
Journal: Journal of Clinical Oncology (2005)

4099 Background: Patients with advanced pancreatic cancer who fail first-line gemcitabine-based therapy have no standard treatment options. Capecitabine (CAPE) has activity in patients with previously untreated pancreatic cancer, and is commonly used in the second line setting. Erlotinib (OSI-774, Tarceva) is a tyrosine kinase inhibitor directed against the epidermal growth factor receptor (EGFR). EGFR is overexpressed in more than 90% of pancreatic cancers and is therefore an attractive treatment target for this malignancy. We performed a phase II study of erlotinib and CAPE in patients with advanced pancreatic cancer who had failed first-line therapy with a gemcitabine-containing regimen. Methods: Eligibility criteria included metastatic pancreatic carcinoma (excluding neuroendocrine tumors), failure of first-line therapy with a gemcitabine-containing regimen, no more than one prior regimen for metastatic disease, and adequate hematologic, renal and hepatic function. Patients received CAPE 1000 mg/m2 PO BID (total dose 2000 mg/m2 QD) for 14 days followed by a one week break, and erlotinib 150 mg PO QD. Treatment cycles repeated every 21 days. Patients were followed for toxicity, response, and overall survival. Results: Thirty patients have been enrolled with the following characteristics: median age 54 (range 41–78); M:F=12:18; ECOG PS 0/1=6/24. Two patients did not initiate protocol therapy. The remaining twenty-eight patients have received a median of 3.8 3-week treatment cycles and are evaluable for toxicity, response, and survival. Treatment was generally well tolerated; the most common grade 3–4 toxicities included: diarrhea 4 (14%); rash 4 (14%); hand-foot syndrome 3 (11%); stomatitis 2 (7%); and thrombosis 2 (7%). Three patients (11%) experienced PR, 16 (57%) experienced stable disease, and 9 (32%) experienced progressive disease as their best response. The median survival time, measured from initiation of protocol therapy is 202 days (6.7 months). Conclusions: The combination of erlotinib and CAPE is associated with antitumor activity and an encouraging median survival time in the second-line treatment of patients with advanced pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI Genentech, Roche
Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3)
Authors: Christopher J Edwards, Francisco J Blanco, Jeffrey Crowley, Charles A Birbara, Janusz Jaworski, Jacob Aelion, Randall M Stevens, Adele Vessey, Xiaojiang Zhan, Paul Bird
Journal: Annals of the Rheumatic Diseases (2016)

To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.Patients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed over 52 weeks.At week 16, significantly more patients receiving apremilast 20 mg twice daily (28%) and 30 mg twice daily (41%) achieved 20% improvement in American College of Rheumatology response criteria versus placebo (18%; p=0.0295 and p<0.0001, respectively), and mean decrease in the Health Assessment Questionnaire-Disability Index score was significantly greater with apremilast 30 mg twice daily (-0.20) versus placebo (-0.07; p=0.0073). In patients with baseline psoriasis body surface area involvement ≥3%, significantly more apremilast 30 mg twice daily patients achieved 50% reduction from baseline Psoriasis Area and Severity Index score (41%) versus placebo (24%; p=0.0098) at week 16. At week 52, observed improvements in these measures demonstrated sustained response with continued apremilast treatment. Most adverse events were mild to moderate in severity; the most common were diarrhoea, nausea, headache and upper respiratory tract infection.Apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks. Apremilast was generally well tolerated and demonstrated an acceptable safety profile.NCT01212770.
Late-breaking abstract: Specific inhalation challenges for the diagnosis of occupational asthma: Importance of occupational rhinitis
Authors: Mael Bellier, Cindy Barnig, Brigitte Sbinne, Jean-Marie Renaudin, Frederic de Blay
Journal: European Respiratory Journal (2014)

Background: Occupational asthma (OA) is the most common occupational respiratory disease. Specific inhalation challenge (SIC) is still considered as the gold standard to confirm the diagnosis of OA.

Objective: To compare characteristics of patients who underwent SIC for possible occupational asthma.

Methods: Data were recorded from 74 subjects with a history of work-related asthma symptoms and who underwent a SIC in our department for possible OA. Positive SIC was defined by an immediate or late drop in forced expiratory volume in one second (FEV1) ≥ 15%, or when following the SIC a significant increase (> 2 doubling doses of metacholine) in non-specific bronchial hyperresponsiveness was measured.

Results: Among the 74 subjects (n=55 women and n=19 men; mean age 40.4 ± 13 years), 33 patients (45%) had a positive SIC including n=26 exposed to low molecular weight (LMW) agents and n=7 exposed to high molecular weight (HMW) agents. Patients with a positive or negative SIC were similar in terms of incriminated sensitizing agent, duration of exposure before onset of asthma, duration of symptoms, smoking habits, baseline FEV1 and atopy. Patients with a positive SIC were also similar for work related conjunctivitis (42.4% vs 36.6%) and dermatitis (21.2% vs 19.5%) when compared to patients with a negative SIC but had significantly more work related rhinitis (84.9% vs 58.53%; p=0.003).

Conclusion: Among patients undergoing SIC for possible occupational asthma, only work related rhinitis was significantly associated with a positive outcome. This underlines the importance of rhinitis in the development of occupational asthma.