tbuckley/cabot-search huggingface dataset:
The diagnostic value of serum glutathione peroxidase 3 levels in patients with early-stage lung cancer.
Authors: In-Jae Oh, Hye-Eun Kim, Seung-Won Lee, Kyu-Sik Kim, Young-Chul Kim, Sang-Hee Cho, Jeong Seon Ryu, Sei-Hoon Yang
Journal: Journal of Clinical Oncology (2014)

e22232 Background: We have selected glutathione peroxidase 3 (GPx3) as a specific candidate that is down-regulated in patients with lung cancer. In this study, we examined the diagnostic value of serum GPx3 which is extracellular protein and readily detectable in blood. Methods: We collected serum samples from 342 patients with lung cancer and 126 controls (normal healthy people and patients with benign diseases or other malignancies). We measured serum GPx3 levels using the enzyme-linked immunosorbent assay. Results: Mean serum GPx3 levels were significantly lower in the patient group as compared with the control group (10.1 ± 5.0 mg/mL vs. 13.0 ± 5.8 mg/mL, P<0.001). In addition, mean serum GPx3 levels were significantly lower in the patients without metastasis as compared with those with metastasis (9.6 ± 4.5 mg/mL vs. 10.7 ± 5.7 mg/mL, P=0.051). Furthermore, mean serum GPx3 levels had a significant correlation with initial treatments (P<0.001). In other words, mean serum GPx3 levels were significantly lower in the surgery group (8.2 ± 4.1 mg/mL) as compared with the concurrent chemoradiotherapy (11.5 ± 4.6 mg/mL, P<0.001), chemotherapy (10.7 ± 5.6 mg/mL, P<0.001) and supportive care groups (10.9 ± 4.8 mg/mL, P=0.002). Conclusions: Our results showed that serum GPx3 levels were significantly lower in the patients who underwent surgery, thus indicating that they may have a diagnostic value in patients with an operable stage of lung cancer rather than those with a locally-advanced or metastatic one.
Totally neoadjuvant chemoradiation therapy with mFOLFOX6 in locally advanced rectal cancer: A single arm phase II study (FOTAC).
Authors: Jianwei Zhang, Yue Cai, Huabin Hu, Jian Xiao, Dianke Chen, Jiayu Ling, Meijin Huang, Lei Wang, Liang Kang, Ping Lan, Jianping Wang, Yanhong Deng
Journal: Journal of Clinical Oncology (2017)

TPS816 Background: Preoperative 5-Fluorouracil based chemoradiotherapy is the standard of treatment for locally advanced rectal cancer. About 15% to 18% of patients would achieve pathologic complete response (pCR) after 5-Fluorouracil based chemoradiation. And the survival outcome of patients with pCR was much better than that of non-pCR. In our previous FOWARC study, in the group of preoperative systemic chemotherapy with mFOLFOX6 combined with radiation, the pCR rate was up to 27.5%. In another study, adding mFOLFOX6 after neoadjuvant chemo radiation in locally advanced rectal cancer improve the pCR rate to 38%. This phase II study aimed to explore whether totally neoadjuvant chemoradiation therapy with mFOLFOX6 could further improve the pCR rate in locally advanced rectal cancer. Methods: The primary endpoint is the pathologic complete response rate (pCR).The secondary endpoint included 3-year disease free survival rate, 3-year local recurrence rate, and safety. We hypothesized that totally neoadjuvant chemoradiation therapy with mFOLFOX6 could improve the pCR rate from 18% to 45% with 5% type I error and 80% power. Fifty patients met inclusion criteria will be enrolled in the trial. All patients will receive long term radiation for 25 times and 50Gy before surgery. Four cycles of mFOLFOX6 would be performed every 2 weeks during radiotherapy, and another 4-6 cycles would be added after radiotherapy and before operation. Totally, the patients will receive 8-10 cycles of chemotherapy before surgery. MRI of the pelvic will be performed every 4 cycles of the therapy to assess clinical response. Then the patient will receive total mesorectal excision at least 8 weeks after radiotherapy. The post-operative chemotherapy will be omitted and all the patients go to surveillance. Clinical trial information: NCT02887313.
Time from surgery to first adjuvant chemotherapy: Experiences at two Toronto hospitals.
Authors: Chanele K. Polenz, Amanda S. Manoharan, Laura Sevick, Christina Marchand, Maha Hassan, Ronald L. Burkes, Christine B. Brezden
Journal: Journal of Clinical Oncology (2013)

e17557 Background: Optimal treatment of patients with colorectal cancer (CRC) includes the timely administration of adjuvant chemotherapy (AC). While Cancer Care Ontario (CCO) guidelines advise that CRC patients receive their first AC no later than 8 weeks after surgical resection, new data suggests treatment should begin between 4 and 6 weeks. This retrospective study was performed to determine the treatment times and identify barriers at two Toronto hospitals: St. Michael’s Hospital (SMH) and Mount Sinai Hospital (MSH). Methods: Of all 797 patients diagnosed with CRC between January 1, 2005 and April 30, 2012 at SMH and MSH, 483 patients did not meet eligibility criteria. Thus, our sample population of 314 patients had stage II or III CRC, and received both surgical resection and AC at each respective hospital. Data collected included: time from surgery to first AC, patient demographics, and systemic/clinical barriers. Data was analyzed using statistical methods in Excel, assuming p-values &lt;0.05 as significant. Results: The mean ageof the patients was 60.5 years (range 23 – 91); 55% were male and 72% had stage III disease; 75% (237/314) had colon cancer and 75% of AC was the FOLFOX regimen. The mean time from surgery to first AC was 57.4 days (sd = 16.8) or 8.2 weeks (range 4.1-18.7). Referral from surgeon averaged 20 days (sd=29.3). Time from medical oncology consult to first AC averaged 26.5 days (sd=30.8) including 23 days awaiting port-a-cath insertion. Post-operative medical complications affected 23.6% of patients. The presence of a complication was associated with delay in AC (10.6 days, p&lt;0.001). An association between tumour site (eg. colon vs. locally advanced rectal cancer) and delay (p=0.0002) was also observed. Conclusions: Adherence to CCO guidelines can be optimized in CRC patients at SMH and MSH. The presence of a medical complication and tumour site are both factors associated with delays in AC treatment post-surgery. To improve the timeliness of care and achieve greater consistency between hospitals, rapid-cycle improvement of confounding barriers will be adopted.
Report of the 13th Annual International Pachyonychia Congenita Consortium Symposium
Authors: L. Rittié, R.L. Kaspar, E. Sprecher, F.J.D. Smith
Journal: British Journal of Dermatology (2017)

The International Pachyonychia Congenita Consortium (IPCC) is a group of physicians and scientists from around the world dedicated to developing therapies for pachyonychia congenita, a rare autosomal dominant skin disorder. The research presented at the 13th Annual Research Symposium of the IPCC, held on 10–11 May 2016, in Scottsdale, AZ, U.S.A., is reported here.
Prognosis of Myelodysplastic Syndromes (MDS) in Patients in the Age of 80 Years and Older: Data from the Regular Care MDS Registry in Germany
Authors: H. Tilman Steinmetz, Roja Wahdat, Burkhard Haastert, Annette Sauer, Bernd Lathan, Christian Lerchenmüller, Hans Tesch, Ulrich Germing, Stephan Schmitz
Journal: Blood (2016)
Rhinovirus species/genotypes and interferon-λ: subtypes, receptor and polymorphisms – missing pieces of the puzzle of childhood asthma?
Authors: Carolina Scagnolari, Fabio Midulla, Raffaella Nenna, Paola Papoff, Guido Antonelli, Alessandra Pierangeli
Journal: European Respiratory Journal (2017)

We agree with Bergauer et al. [1]: in order to understand and manage asthma it is necessary to characterise better the virological and immunological factors associated with exacerbation events. In their article, those authors indicated that human rhinovirus (HRV) infection may regulate type I and III interferon (IFN) expression/production in paediatric asthma, both at baseline and during disease exacerbations. Although these findings are interesting and meaningful, we are concerned about some shortcomings in their experimental design and discussion that might lead to misleading conclusions. Rhinovirus and interferon-λ: missing pieces of the puzzle of childhood asthma <http://ow.ly/vBL9308zN20>
Ratio of total leucocyte count to C-reactive protein: Does it help differentiate engraftment fever from infective fever in patients undergoing autologous stem cell transplant?
Authors: Sachin Punatar, Anant Gokarn, Deepan Rajamanickam K., Alok Gupta, Libin Mathew, Sadhna Kannan, Navin Khattry
Journal: Journal of Clinical Oncology (2015)

7032 Background: Engraftment fever (EF) is common in 2ndweek post autologous hematopoietic stem cell transplant (auto HSCT). It is difficult to differentiate from infective fever (IF). This leads to unnecessary use and cost of antibiotics. Also timely treatment of EF may prevent progression to full blown engraftment syndrome (ES). We studied the role of total leucocyte count (TLC) to C-reactive protein (CRP) ratio in differentiating EF from IF. Methods: Consecutive patients with breakthrough fever (BF) from d+7 to d+15 post auto HSCT, from March 2011 to August 2013, were included in this retrospective analysis. BF was defined as new onset fever preceded by an afebrile period of at least 48 hours. BF episodes were classified as IF or EF. Fever was classified as IF if blood culture was positive, or there were radiological signs of infection or if fever subsided within 48 hours of change of antibiotics. EF was defined as fever associated with rising counts without any identifiable infective focus responding to steroids. Antibiotics were added at the onset of BF. If fever persisted beyond 48 hours and no infective cause was identified, systemic steroids were started. Daily morning TLC and CRP values were obtained from patients’ records. TLC:CRP ratio was calculated from day of admission to day of discharge. Optimal cut-off value of the ratio on the day of BF was obtained by plotting a receiver operating curve. Sensitivity and specificity were calculated. Results: Seventy patients had BF of 110 auto HSCT patients. Nineteen had multiple myeloma, 50 had lymphoma and 1 neuroblastoma. Median day of neutrophil and platelet engraftment was 10 and 13 respectively. The median day of BF was 9. Sixty two patients had EF, among whom 15 had ES. We found an optimal value of 0.056 for differentiating between IF and EF. Using a ratio > 0.056 for diagnosing EF, sensitivity and specificity were 63% (95% CI – 50 – 75%) and 100% (95% CI – 63 – 100%) respectively. Conclusions: In 2nd week post auto HSCT, a value of the ratio of TLC:CRP > 0.056 on the day of BF is highly specific for EF. Prospective studies are warranted to confirm the results. This could help reduce unnecessary use and cost of antibiotics.
Hypofractionated (HRT) versus standard (SRT) radiotherapy with or without temozolomide (T) for elderly patients with glioblastoma (GBM).
Authors: Shyam Kumar Tanguturi, Patrick Y. Wen, David A. Reardon, Eudocia Quant Lee, Lakshmi Nayak, Laura W Christianson, Margaret C Horvath, Ian F. Dunn, Alexandra J Golby, Mark D Johnson, Elizabeth B Claus, E. Antonio Chiocca, Keith L. Ligon, Brian Michael Alexander, Nils D. Arvold
Journal: Journal of Clinical Oncology (2014)

2065 Background: No randomized trials among elderly GBM patients using HRT have compared efficacy to the Stupp regimen of SRT+T, and many elderly patients in the United States receive SRT+T. Methods: We evaluated 88 consecutive patients ≥ 65 years old with GBM diagnosed from 1994-2010 who received HRT or SRT with or without concurrent T. Overall survival (OS) was calculated by the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model and Fisher exact test. HRT consisted of 40 Gy/15 fractions, and SRT consisted of 59.4-60 Gy/30-33 fractions. Results: Patients received SRT+T (n = 26), SRT (n = 35), HRT+T (n = 21), or HRT (n = 6). Median age was 70 among SRT±T patients and 80 among HRT±T patients (P < 0.001), KPS was lower among HRT±T patients (P < 0.001), and SRT-alone patients were more likely to be treated prior to the year 2000 (P < 0.001); there were no significant differences between groups with regard to gender, tumor size or multifocality, extent of resection, or MGMT methylation status. With a median follow up of 9.7 mo, median OS was 10.1 mo (SRT+T), 9.5 mo (SRT), 10.8 mo (HRT+T), and 3.0 mo (HRT). On multivariate analysis, compared to SRT+T, mortality was significantly lower for HRT+T (AHR = 0.39; 95% CI, 0.16-0.91; P = 0.030) and higher for HRT (AHR = 3.94; 95% CI, 1.16-13.42; P = 0.028). Increasing age (AHR = 1.08; 95% CI, 1.01-1.15; P = 0.018), lower KPS (AHR = 1.03; 95% CI, 1.01-1.04, P = 0.002), and multifocal tumors (AHR = 3.18; 95% CI, 1.57-6.46; P= 0.001) were also associated with higher mortality. Conclusions: Among elderly GBM patients, HRT+T was associated with improved survival compared to SRT+T, despite older age and lower KPS at baseline. These data suggest that with the addition of T, the number of radiotherapy treatments may be reduced by half with no decrement in survival, and should be explored in a randomized setting.
Prognostic value of etoposide area under the curve (AUC) in lymphoma patients treated with BEAM regimen and ASCT: Multicenter study of Groupe d’Etudes des Lymphomes de l’Adulte (GELA).
Authors: Olivia Bally, Gilles Freyer, Gilles A. Salles, Anne-Sophie Michallet, Olivier Casasnovas, Herve Tilly, Vincent Ribrag, Catherine Sebban, Claire Falandry, Benoit You
Journal: Journal of Clinical Oncology (2012)

8068 Background: The prospective LYMPK study primary objective was to assess the impact of etoposide pharmacokinetic (PK) parameters on toxicity and efficacy in lymphoma patients receiving the BEAM regimen (carmustine, cytarabine, etoposide and melphalan) followed by autologous stem cell transplant (ASCT). We previously showed the high inter-individual variability in etoposide PKs, defined by area under the curve (AUC) and trough concentration (Cmin), among study patients treated with the same doses /m 2 (You B et al, Proc. ASCO 2008). Methods: Ninety-six patients with malignant lymphoma at 1st line (n=52) or relapse (n=44) were enrolled in 5 centers. All received BEAM regimen, including high-dose etoposide (100 to 200 mg/m 2 bid for 4 days), followed by ASCT. Individual etoposide AUC and Cmin were estimated by population PK approach using NONMEM program. The impact of PK parameters on toxicity and survival was assessed using linear regression and univariate/multivariate analyses. Results: Data from 90 patients were assessable after a 4.2-year median follow-up. The bi-compartment model previously reported was used to characterize PK parameters (You B et al, Proc. ASCO 2008). Etoposide AUC and Cmin correlated with mucositis duration, especially for grade 3-4 toxicity (p&lt; 0.05), but not with other toxicities. Cmin had significant prognostic value regarding 5 year progression free survival (p=0.03). Five year overall survival (OS) was longer in patients with higher AUC (76% vs 56%, if AUC &gt; median, p=0.04) as it was in patients with higher Cmin (78% vs 54%, if Cmin &gt; median, p=0.02). When assessed with available IPI prognostic factors (age; performance status; LDH and stage) using Cox analysis, the only independent prognostic factors of OS and disease specific survival were etoposide AUC (HR= 0.39, 95% CI = 0.16-0.94) and Cmin (HR = 0.32, 95% CI = 0.12-0.80). Conclusions: LYMPK study results suggest that individual etoposide systemic exposure has a strong impact on survival in lymphoma patient receiving BEAM regimen and ASCT. Given the high variability in patient AUCs, plasma concentration-based adjustment of etoposide dose may be considered in future studies.
Hepatitis C virus–induced CCL5 secretion from macrophages activates hepatic stellate cells
Authors: Reina Sasaki, Pradip B. Devhare, Robert Steele, Ranjit Ray, Ratna B. Ray
Journal: Hepatology (2017)

Hepatitis C virus (HCV)-mediated chronic liver disease is a serious health problem around the world and often causes fibrosis/cirrhosis and hepatocellular carcinoma. The mechanism of liver disease progression during HCV infection is still unclear, although inflammation is believed to be an important player in disease pathogenesis. We previously reported that macrophages including Kupffer cells exposed to HCV induce proinflammatory cytokines. These secreted cytokines may activate hepatic stellate cells (HSCs) toward fibrosis. In this study, we examined crosstalk between macrophages and HSCs following HCV infection. Primary human HSCs and immortalized HSCs (LX2 cells) were incubated with conditioned medium derived from HCV-exposed human macrophages. Expression of inflammasome and fibrosis-related genes in these cells was examined, with increased expression of inflammatory (NLR family pyrin domain containing 3, interleukins 1β and 6, and cysteine-cysteine chemokine ligand 5 [CCL5]) and profibrogenic (transforming growth factor β1, collagen type 4 alpha 1, matrix metalloproteinase 2, and alpha-smooth muscle actin) markers. Further investigation suggested that CCL5, secreted from HCV-exposed macrophages, activates inflammasome and fibrosis markers in HSCs and that neutralizing antibody to CCL5 inhibited activation.Together, our results demonstrate that human macrophages exposed to HCV induce CCL5 secretion, which plays a significant role in hepatic inflammation and fibrosis. (Hepatology 2017;66:746-757).
Phase II open clinical trial to evaluate efficacy and safety of neoadjuvant trastuzumab in HER2-positive locally advanced breast cancer (LABC)
Authors: C. H. Arce-Salinas, F. U. Lara, E. Leon
Journal: Journal of Clinical Oncology (2009)

592 Background: LABC in Mexico represents between 50–60% of the new diagnosed cases, and 25–30% of those cancers are HER-2/neu positive. Primary systemic therapy trastuzumab-based combination chemotherapy (ChT) has shown clinical benefit and pathologic complete response rates are obtained between 17%-67%. The aim of this study was evaluate the complete pathologic response (pR) rate with the combination of four cyles of FAC (5FU/Doxorubicin/Cyclophosphamide) followed by weekly paclitaxel (PTX) and trastuzumab. As secondary endpoint was evaluate cardiac safety. Methods: All patients with LABC HER-2 positive (IHC 3+ or FISH amplification) with stages IIb-IIIc were included, patients with palpable nodes underwent fine needle aspiration to confirm metastatic nodal disease (MND), other inclusion criteria was FEVI ≥55% determined by MUGA, hematologic, renal and hepatic function normal. We exclude inflammatory breast cancer. All patients received 4 cycles of FAC followed by weekly PTX (80 mg/m 2 ) concomitantly with trastuzumab, 2 mg/kg, at the end of treatment surgery was performed, and pR was evaluable. Complete pR was defined as the absence of tumor cells in breast and axillary nodes. Disease free survival (DFS) was calculated with Kaplan-Meier method. Protocol was approved by local ethical committee. NCT 00533936. Results: We included 92 patients, median age was 48 (27–68) yrs. Median tumor size was 6 (5.4–6.5) cm, 84.9% had MND. Efficacy analysis was made in 71 patients; 21 patients are still under treatment. Overall clinical response was reached in 71% (complete 37% and partial 42%). Eleven patients were considered inoperable (skin affection, larger size &gt; 5 cm or fixed to chest wall and received radiotherapy 50 Gy). Complete pR was reported in 48% of cases. Median follow-up was 17.4 (CI95% 14.9, 17.6) mo and media of DFS was 25.1 (CI95% 23.5, 26.7) mo. We found cardiac toxicity (CT) grade 3 in 1.1%, and grade 2 in 3.2%. Conclusions: Combination of PTX and trastuzumab after 4 cycles of FAC is highly active in terms of complete pR. This scheme was tolerated, with CT grade 3–4 in less than 2%. No significant financial relationships to disclose.
Docetaxel (Do) and gemcitabine (Gem) in advanced pancreatic cancer (APC) patients (pts): A multicentre study
Authors: G. Des Guetz, L. Chauvenet, D. Paraiso, D. Mayeur, T. Aparicio, E. Chirat, C. Boiron, C. Bouleuc-Parrot, E. Pujade- Lauraine
Journal: Journal of Clinical Oncology (2007)

15065 Background: Gem is the only approved chemotherapeutic drug in the treatment of APC. Do as single agent has shown some activity. Effective cytotoxic combinations with gem are urgently needed. Methods: Combination of Gem 1200 mg/m 2 /d1 + Do 50 mg/m 2 /d1 every 2 weeks was evaluated in first line APC pts with Karnovsky Index (KI) &gt; 40, and good organ function. Initial Do dose was modified according to liver biology alterations. Treatment of relapse with Gem-Do or other combinations was allowed. Results: The 45 pts (male=64%) included in 7 centres had a median age of 62 yrs (range 36–81 yrs) and 26 (58%) had metastatic disease. Pts received a median of 4 cycles (0–6) with a median dose of 47 mg/m 2 for Do and 1170 mg/m 2 for Gem. Neutropenia Gr 3/4 was the most severe toxicity (Tox) (24% of pts) and required G-CSF support, with infection G3 in 14 pts (31%), febrile neutropenia in 1. Others G3 Tox were fatigue (20% of pts), diarrhea (14%), anemia (9%) thrombopenia (7%) and G2 Tox: alopecia (33%), nausea (15%) and edema (11%). During treatment, KI improved or was stable in 33% and 44% of pts, weight increased or was stable in 38% and 23%, pain control was better or stable in 20% and 56%. After panel review, objective RECIST response was observed in 17.7% of pts (CR = 4.4%) and stable disease in 40%. Median progression- free survival (PFS) was 3.8 months (mo) and 14 pts (31%) had PFS between 6 and 14 mo. Median survival was 12.0 mo (95% CI; 10.2–13.8 mo). Conclusions: The combination of Do and Gem every 2 weeks is feasible and should be associated with systematic growth factor support. Subjective and objective criteria of efficacy in APC are encouraging. A direct comparison with Gem single agent is warranted. No significant financial relationships to disclose.