tbuckley/cabot-search huggingface dataset:
Incidence of bleeding and thrombosis among elderly patients (pts) undergoing systemic chemotherapy in advanced non-small cell lung cancer (NSCLC): An analysis of North Central Cancer Treatment Group (NCCTG) trials.
Authors: Y. Qi, G. K. Dy, G. D. Nelson, S. E. Schild, S. J. Mandrekar, A. A. Adjei
Journal: Journal of Clinical Oncology (2010)

e18093 Background: Elderly pts receiving platinum-based doublet chemotherapy for advanced NSCLC derive similar therapeutic benefit as younger pts. However, elderly pts experienced more bleeding without obvious survival benefit compared to younger pts when bevacizumab was added to a carboplatin paclitaxel doublet. We investigated the incidence risks of grade 3+ bleeding and thrombotic events in advanced NSCLC pts from NCCTG chemotherapeutic trials. Methods: Individual pt data from 10 trials (n = 698) were pooled. Incidence risks of grade 3+ treatment related thrombosis or hemorrhage were estimated for the entire cohort as well as by age group (grp) (< 65 vs. ≥ 65 year old [yo]) and by treatment grp (platinum-based regimen [PBR] or vascular endothelial growth factor inhibitors [VEGFI]). Logistic regression models (adjusted for age grp) were used to examine the relationship between treatment grp (PBR or VEGFI) and risk of grade 3+ events. Odds ratio (OR) and 95% confidence interval (CI) are reported. Results: 30% of pts received PBR, 20% received VEGFI, and 61% of pts were ≥ 65 yo. Overall incidence of grade 3+ thrombosis and grade 3+ hemorrhage was 3.3%, and 1.3% respectively. There were no significant differences in thrombotic events by age or treatment grp. Pts who received PBR were more likely to experience grade 3+ hemorrhage (2.4% vs. 0.8%; OR [95% CI] = 3.4 [0.9-13.5]). The risk was lower among pts ≥ 65 yo (age-specific OR was 4.9 in pts < 65 and 2.5 in pts ≥ 65 yo). Exposure to VEGFI increased the risk of hemorrhage (3.6% vs. 0.7%; OR [95% CI] = 5.2 [1.4-20.0]) though this was more marked in elderly (age-specific OR was 3.2 in pts < 65 and 7.8 in pts ≥ 65 yo). Among the 30% patients who received PBR (n = 207), addition of VEGFI further increased the risk of hemorrhage (incidence was 6.3% in VEGFI plus PBR pts and 0.7% in PBR only pts). Conclusions: PBR and VEGFI appear to increase the risk of bleeding in both younger and elderly pts. The risk of thrombotic events is not significantly affected. Due to the small effective sample size of this study, further exploration is needed for a definite conclusion. No significant financial relationships to disclose.
Assessing two meta-analysis (MA) methods: Individual patient data-based (IPD) versus literature-based abstracted data (AD) in 10 MA including 37,002 patients (pts)—Are there differences of concern?
Authors: E. Bria, R. J. Gralla, H. Raftopoulos, I. Sperduti, M. Milella, F. Cognetti, D. Giannarelli
Journal: Journal of Clinical Oncology (2011)

6054 Background: MA are widely used in evidence-based medicine (EBM); whether the two most frequently used methods (IPD, AD) provide equally reliable results is debated. Here we analyzed the conclusions achieved by each method using the same panel of studies, weighing agreement/discrepancy and evaluating predictivity of AD results with respect to IPD using multiple methods. Methods: 10 different settings (Table) subjected to IPD were selected to also conduct AD. Hazard and risk ratios (Rs) with 95% confidence intervals (CI) were derived. Methods agreement was analyzed (Blant-Altman method) as difference or ratio and compared using variance-ratio (F-test) and concordance correlation coefficient (CCC). Correlations between AD/IPD-Rs were estimated with linear regression [Pearson (r), R2 coefficients, Spearman-Rho/Kendall-Tau coefficients] to derive a predictive estimation of AD on IPD. Results: 14 outcomes in 10 MAs (37,002 pts) were analyzed (Table). Graphical comparison with the B-A method did not show meaningful differences between AD and IPD (mean difference 0.0075, 95% CI -0.0052, 0.02), without significant discrepancy, with no significant differences in variance (F-test 1.06, p=0.91), and high CCC (0.98, 95% CI 0.59, 0.99). A highly significant correlation by both parametric and nonparametric tests allowed derivation of a linear regression equation able to predict IPD results from AD data (YAD=[0.04315] + XIPD[0.958]; R2 0.97). Conclusions: Analysis of MAs conducted by AD or IPD methods showed: 1) no significant differences between the 2 MA methods; 2) AD results predict IPD results, without significant risk of overestimation. Setting Pts (AD/IPD) Rs (AD/IPD) Bladder 458/491 0.76/0.75 Breast 3,672/4,006 0.71/0.71 Breast 2,805/3,034 0.94/0.92 0.99/0.95 Breast 11,163/9,856 0.77/0.77 0.98/0.94 Breast 8,794/9,015 0.73/0.71 0.80/0.79 Breast 2,695/2,447 0.68/0.64 0.95/0.97 Lung 4,658/4,584 0.90/0.89 Lung 778/778 0.71/0.73 Lung 857/865 1.06/1.09 Emesis 1,926/1,926 0.998/1.00
PEG Modified rVWF Prolongs the Survival of Native rFVIII in Hemophilia A Knock-Out Mice.
Authors: Peter L. Turecek, Friedrich Scheiflinger, Herbert Gritsch, Bernhard Baumgartner, Katalin Váradi, H. Peter Matthiessen, Juergen Siekmann, Eva-Maria Muchitsch, Hans Peter Schwarz
Journal: Blood (2006)
Algorithm for identifying various second- and third-line chemotherapy regimens in elderly U.S. Medicare patients with metastatic colon cancer.
Authors: Kaloyan A Bikov, C. Daniel Mullins, Ebere Onukwugha, Brian S. Seal, Nader Hanna
Journal: Journal of Clinical Oncology (2013)

553 Background: Patients with metastatic colon cancer (mCC) often receive multiple lines of chemotherapy treatment (TX) in response to disease progression or toxicities. A claims-based algorithm that identifies TX lines can provide information on “real world” clinical practice patterns that may not be captured by clinical trials. Methods: Our claims-based algorithm was applied to SEER-Medicare data of elderly mCC patients diagnosed in ‘03-‘07 and followed through ‘09. The algorithm included 17 clinical rules for identifying the beginning and end TX lines. The face validity of the algorithm was assessed by 1) examining the output against a TX map for a random sample of patients; 2) evaluating the overall results; and 3) conducting a sensitivity analysis, which evaluated the variability in the number of detected TX lines as a function of key algorithm parameters. Results: Of 7,951 mCC patients, 3,266 (41%) received TX; 1,440 (18% of all, 44% of TX) and 274 (3% of all, 8% of TX) received 2nd and 3rd line TX, respectively. Fewer than 1% of treated patients had a 4th TX line. The utilization patterns in terms of number and type of TX lines were robust to changes in the algorithm parameters. OX±BEV (45%), 5FU/LV±BEV (33%) and IRI±BEV (16%) were the three most common initial TXs. 2nd line TX most commonly consisted of IRI±BIOLOGIC (62%) and OX±BIOLOGIC (26%), but 6% of patients received only BIOLOGICS. CETUX (19%), PANIT (15%), IRI alone (17%) and OX alone (12%) were the most common 3rd line TXs. OX to IRI (49%), IRI to OX (14%), 5FU/LV to OX (12%), and 5FU/LV to IRI (12%) were the most frequent TX progressions for those with 2nd line TX. 5FU/LV to OX to IRI (26%), OX to IRI to BIOLOGICS alone (25%), 5FU/LV to IRI to OX (14%) and IRI to OX to BIOLOGICS alone (6%) were the most frequent TX progressions for those with 3rd line TX. Conclusions: Our claims-based algorithm suggests that during 2003-2009 relatively few elderly mCC patients received 2nd and 3rd line TX. Sensitivity analysis confirmed the robustness of the algorithm. Future observational studies should address the “real world” benefits and risks of 2nd and 3rd line TX among elderly mCC patients.
Cisplatin (CDDP) and oral vinorelbine (NVBO) concomitantly with radiotherapy (RT) after induction chemotherapy (CT) in locally advanced (LA) non-small cell lung cancer (NSCLC) treatment: Clinical experience in five institutions in Spain.
Authors: J. Remon, I. Diaz Padilla, J. Andrade, A. Gasco, J. M. Jurado, F. J. Perez, M. P. Lianes
Journal: Journal of Clinical Oncology (2010)

7093 Background: CDDP+NVBO as induction and concomitant regimen with RT has shown good efficacy outcomes and safety profile (Krzakowski, J Thor Oncol. 2008). Five Spanish institutions have collected the data of patients with LA NSCLC treated with the previously reported regimen in order to confirm the results in the clinical daily activity. Methods: Between February 2007 and April 2009, 19 chemo-naïve patients (p) with histologically confirmed stage IIIA/IIIB unresectable LA NSCLC were treated. Treatment consisted of NVBO D1,8 60 mg/m2 cycle (cy) 1 and 80 mg/m2 cy 2 (if no haematological/non- haematological grade 3-4 toxicity) and CDDP 80 mg/m2 every 3 weeks for 2 cy as induction. OR/NC pts received NVBO D1,8 40 mg/m2 and CDDP 80 mg/m2 every 3 weeks for 2 more cy and RT 60-66 Gy in 6.5 weeks. Results: Patient's characteristics were: Median age, 61 years (range 50-76); all males; smokers, 79%; adenocarcinoma, 42% / squamous, 26%; stage IIIA, 5% / IIIB, 95%. 17 p completed the 4 cy treatment; Treatment was cancelled in 1 p after cy 1 due to neutropenia, and 1 p died after cy 3 (due to disease). We analyzed 72 cy. Hematological toxicities (% cy): grade (g) 3/4 neutropenia, 9.7%; g3 anemia, 1.4%. Non-hematological toxicities (% cy): oesophagitis g 3/4, 1.4%; constipation g4, 1.4%; fever g3, 1.4%; infection g3, 4.2%. No nausea or vomiting g 3/4 were reported. 17 p were evaluable for response. 13 PR (76.5%) and 2 SD (11.8%) were reported. Survival analysis has not been performed due to short follow-up. Conclusions: The findings of this retrospective analysis confirm the previously reported outcomes of efficacy and safety with NVBO plus CDDP when administered as induction and concurrently with RT in stage IIIA/IIIB p. The excellent tolerance profile allowed to complete the CT/RT treatment in 90% of pts. No significant financial relationships to disclose.
One-stop navigation for cancer support: Assisting unmet needs according to own initiatives.
Authors: S. C. K. Lee, C. Wang, C. Hsieh
Journal: Journal of Clinical Oncology (2011)

e16636 Background: Cancer support needs are with complexity, individual specific and access demanding. That how to bridge unmet needs to appropriate supports and to solve issues in a prompt and individualized manner is challenging. Cancer is the leading cause of death in Taiwan and cancer survivors are increasing. Patient navigation program is a national initiative; and one-stop cancer navigation programs in ambulatory settings led by trained oncology nurses or social workers were piloted in 5 hospitals aiming to address unmet cancer needs. The purpose of this study was to explore the programs and describe the unmet needs and navigation activities. Methods: All navigation programs were at outpatient settings where the patients can easily access. Trained lay persons or volunteers were accompanied the professional navigators to assist in the program. The sites were equipped with educational materials and necessities for cancer support. A retrospective analysis was conducted based on the professional navigators’ records of each encounter from 2008 to 2009. Data included characteristics of the patients/family, reported unmet needs, type of activities provided, length of the encounter. Results: A total of 4620 encounters was recorded. They were for the patients with mean age of 48.3 and with the mean length of 20 minutes. A majority of them were made for female patients (56.9%), by the patients’ own initiatives (74.4%) and for the issues related to follow-up treatment. The breast (29.0%) and oral (17.0%) cancer diagnoses were accounted as the top two. Greater than 1/3 were unmet needs of psychosocial, disease issues, care or nutrition issues. The top 3 activities provided by navigators were education, counseling and providing information/booklets. Around 1/3 included subsequent bridges to other resources or providing rehabilitation necessities, such as wits, bra. The length of encounters was significantly longer if the unmet needs were emotional support, patient education for newly diagnosis and bridging to other resources. Conclusions: One-stop cancer navigation programs in ambulatory settings provided an alternative way to fulfill cancer patients’ unmet needs based on their own initiatives.
Meet the First Authors
Authors: Farid Khalafalla, Galal Khalafalla
Journal: Circulation Research (2017)

Farid's goal is to establish an independent research career with emphasis on studying cellular responses to extracellular nucleotide stress signals in the myocardium and developing novel translational approaches for treatment of HF.In his spare time, Farid enjoys attending lectures in Islamic studies, playing soccer, and traveling with his friends, family, and 6-month-old baby.
Percutaneous thermal ablation of medium and large hepatocellular carcinoma: Long-term outcome and prognostic factors
Authors: X. Yin, X. Xie, M. Lu, H. Xu, Z. Xu, M. Kuang, G. Liu, J. Liang, W. Lau
Journal: Journal of Clinical Oncology (2008)

15572 Background: To evaluate therapeutic efficacy of percutaneous thermal ablation with curative intention for hepatocellular carcinoma(HCC) between 3.0cm and 7.0cm. Methods: Percutaneous radiofrequency ablation or microwave ablation were employed to treat 109 HCC patients with at least one tumor between 3.0cm and 7.0cm. Fifty-eight patients received thermal ablation as the first treatment, and the remaining 51 were treated for post-hepatectomy recurrent HCC. Eighty-nine patients had main tumor 3.0–5.0 cm, and 20 patients 5.0–7.0 cm. Local therapeutic efficacy, long-term outcome and prognostic factors were analyzed. Results: There were no treatment-related deaths, and major complication rate was 9.2%. Complete ablation was achieved in 92.6% patients. Local tumor progression occurred in 22% patients. Distant recurrences developed in 53.2% patients. 1-, 3-, 5- year survival rates were 75.8%, 30.9% and 15.4%, respectively. Univariate analysis showed that incomplete tumor ablation, post-hepatectomy recurrence and pre-ablation AFP ≥200 ng/ml were three unfavorable prognostic factors for long-term survival (p=0.000, 0.015, 0.008, respectively). Cox regression analysis confirmed that incomplete tumor ablation, recurrent tumors and pre-ablation AFP ≥200 ng/ml were independent unfavorable prognostic factors, with an exp(B) of 4.158 (p=0.001), 1.568 (p=0.082), 1.593 (p=0.082), respectively. Conclusions: Percutaneous thermal ablation was effective and safe in treating HCC between 3 and 7cm, with acceptable local tumor control and long-term outcomes. No significant financial relationships to disclose.
Ixazomib-Lenalidomide-Dexamethasone (IRd) Combination before and after Autologous Stem Cell Transplantation (ASCT) Followed By Ixazomib Maintenance in Patients with Newly Diagnosed Multiple Myeloma (NDMM): A Phase 2 Study from the Intergroupe Francophone Du MyéLome (IFM)
Authors: Philippe Moreau, Cyrille Hulin, Denis Caillot, Gerald Marit, Aurore Perrot, Laurent Garderet, Thierry Facon, Lotfi Benboubker, Lionel Karlin, Mourad Tiab, Bertrand Arnulf, Jean-Paul Fermand, Xavier Leleu, Cyrille Touzeau, Murielle Roussel, Lucie Planche, Stephane Minvielle, Marie-Christine Bene, Herve avet-Loiseau, Thomas Dejoie, Michel Attal
Journal: Blood (2016)
Analysis of survival after disease progression in patients with renal cell carcinoma (RCC) who failed treatment with sunitinib.
Authors: M. Miscoria, S. Pirrie, S. Baijal, A. Tew, N. D. James, E. Porfiri
Journal: Journal of Clinical Oncology (2011)

e15154 Background: We analysed the survival after progression (SAP) of 112 sunitinib treated RCC patients in order to identify risk factors associated with SAP which could be used for counselling and to select patients suitable for 2nd line therapy. Methods: RCC patients who progressed whilst on sunitinib were included in the study. SAP was calculated using the Kaplan-Meier method from the time of progression until death. Univariate analysis investigating 15 potential risk factors for reduced SAP was conducted. Factors which were significant at the 0.05 level univariately were included in multivariate modelling using Cox Proportional Hazards. Results: 112 consecutive RCC patients who progressed on sunitinib were identified. Median age was 59 years (31-85), M/F 84/28, median time from diagnosis to treatment 12 months, 85 (76%) patients had ECOG PS 0-1, 87 (78%) had a previous nephrectomy, 40 (36%) had previous immunotherapy and 10 (9%) targeted therapy. The median time to progression on sunitinib was 8.1 months. The median SAP was 4.1 months (95%C.I. 3.2 – 5.9). 22 patients (20%) had a SAP ≥ 1year. 9 risk factors were associated with SAP in univariate analysis but the only risk factors independently associated with improved SAP in multivariate analysis were: duration of sunitinib treatment prior to progression ≥ 1year, ECOG PS 0-1, only 1 metastatic site. There were 16 patients with the 3 favourable risk factors: 9 patients had a SAP > 12 months and 11 had overall survival of more than 2 years. 2nd line treatment was not available from the UK National Health Service at the time of the study therefore 50 (45%) patients continued on sunitinib after progression for a median of 3.3 months because of persistent clinical benefit. These patients had a median SAP of 11.6 months (95%C.I. 5.6 - 14.6). Conclusions: The median survival of our cohort of patients was very short after the failure of sunitinib however risk factor analysis was able to identify a subset of patients with a longer SAP who may benefit from 2nd line therapy. Interestingly the patients who remained on sunitinib after progression also had a better SAP perhaps as a result of residual drug efficacy or because of favourable clinic characteristics.
A matched pair analysis of five-fraction stereotactic body radiation therapy versus protracted conventional radiation therapy in patients receiving chemotherapy for locally advanced pancreatic cancer.
Authors: Antony Koroulakis, Petra Prins, Andrew Gabrielson, Chris Silveri, Andrew Hwang, Saman Abdulkadir, Brianna McCullough, John Marshall, Michael J. Pishvaian, Aiwu Ruth He, Brandon George Smaglo, Sean P. Collins, Keith Robert Unger
Journal: Journal of Clinical Oncology (2016)

444 Background: Stereotactic body radiation therapy (SBRT) is a novel treatment modality for unresectable, locally advanced pancreatic cancer (LAPC). SBRT delivers high doses of radiation over a shorter duration, with minimal acute toxicities, compared with conventional radiation therapy (CRT) using intensity modulated radiation therapy (IMRT) or 3D conformal techniques (3D-CRT). Few studies have compared outcomes between SBRT and CRT techniques. We conducted a retrospective matched pair analysis of LAPC patients receiving chemotherapy and either SBRT or CRT to assess local control (LC), progression-free survival (PFS), and overall survival (OS). Methods: We retrospectively analyzed 28 patients with LAPC who were treated between August 2006 and August 2014 with 5-FU- or gemcitabine-based chemotherapy combined with CRT (45–56 Gy over 25–28 fractions) or SBRT (25–30 Gy over 5 fractions). Fourteen patients treated with CRT were matched with 14 patients treated with SBRT for age (&lt; 65 vs. ≥ 65 years); nodal staging (N0 or N1); and chemotherapy type (gemcitabine-based or 5-FU-based, administered either concurrently or as induction therapy). Tumor response was assessed using RECIST and all outcomes were calculated from the date of diagnosis. The Log Rank test of Kaplan-Meier curves was used for statistical analyses. Results: Median follow-up time was 11 months (mo). The median duration of LC, PFS, and OS for the entire cohort was 11, 8, and 14 mo, respectively. Median duration of LC was 10 mo for CRT and 11 mo for SBRT (p &gt; 0.05). Median PFS was 8 mo for both groups (p &gt; 0.05). The median OS times were 12 mo for SBRT and 16 mo for 3D-CRT/IMRT (p &gt; 0.05). Conclusions: In this small matched-pair analysis, LAPC patients treated with chemotherapy had similar outcomes following 5 fractions of SBRT as compared with a protracted course of CRT. Given the shorter treatment duration with SBRT, further study is warranted with increased cohort sizes and stratification by other patient and disease characteristics.
A phase I/II study of DHP107, a novel oral paclitaxel formulation, in patients with advanced solid tumors (phase I) and gastric cancer (phase II).
Authors: Min-Hee Ryu, Baek-Yeol Ryoo, Tae Won Kim, Sung-Bae Kim, Hyeong-Seok Lim, Kyun-Seop Bae, Sook Ryun Park, Yeong-Woo Jo, Hyun Ju Cho, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2014)

101 Background: Paclitaxel has been proven to be effective and widely used in various types of cancers. DHP107 is a novel oral paclitaxel formulation. In the previous first-in-human study, DHP107 showed no DLTs at a single dose-escalating schedule and was reported safe and feasible in patients with advanced malignancies. This study was conducted to determine 1) recommended dose (RD) for multiple dosing of DHP107 in patients with metastatic solid tumor and 2) efficacy in patients with advanced gastric cancer (AGC). Methods: In phase I study, standard 3 + 3 dose escalation scheme was used, and the planned dose of DHP107 was 150 mg/m 2 bid at level 1, 200 mg/m 2 bid at level 2, and 250 mg/m 2 bid at level 3 on days 1, 8, and 15, every 4 weeks. In phase II study planned by Simon’s optimal two stage design (P 0 =0.05, P 1 =0.25, α=0.05, and β=0.2), DHP107 was administered at the RD in patients with AGC refractory to first-line chemotherapy containing fluoropyrimidine and platinum. Results: In the phase I study, no dose-limiting toxicity (DLT) was observed at level 1 (n=3) and at level 2 (n=6). At level 3, 2 out of 4 patients showed a DLT (one grade 4 neutropenia over 7 days and one febrile neutropenia). At additional dose level 2A (225 mg/m 2 bid), 2 out of 4 patients experienced febrile neutropenia. Finally, the RD of DHP107 was determined as level 2 (200 mg/m 2 bid). In PK analysis, 200 mg/m 2 bid of DHP107 showed similar AUC, C max and half-life to i.v. paclitaxel at 80 mg/m 2 . Out of the 11 patients enrolled in the phase II study, 3 patients achieved a confirmed partial response (27%; 95% C.I. 0-59%). Grade 3/4 adverse events with frequency &gt; 5% included neutropenia (27.3%), stomatitis (18.2%), anemia (9.1%), and febrile neutropenia (9.1%). There was no treatment-related death. Conclusions: RD of DHP107 was determined as 200 mg/m 2 bid. At the RD, DHP107 was generally well tolerated and showed anti-tumor activity comparable to i.v. paclitaxel as a second-line chemotherapy in AGC. Based on these results, a phase III study to compare DHP107 with i.v. paclitaxel is currently ongoing in AGC. This study was supported by DAEHWA Pharmaceutical Co. and Gangwon Institute for Regional Program Evaluation by Korean government.