tbuckley/cabot-search huggingface dataset:
Contrast-enhanced T1-weighted subtraction maps for response assessment in recurrent glioblastoma treated with bevacizumab.
Authors: Benjamin M. Ellingson, Hyun J. Kim, Davis C. Woodworth, Whitney B. Pope, Jonathan N. Cloughesy, Robert J. Harris, Albert Lai, Phioanh L. Nghiemphu, Timothy F. Cloughesy
Journal: Journal of Clinical Oncology (2013)

2055 Background: Antiangiogenic therapy in glioblastoma (GBM) results in decreased enhancement on post-contrast T1w images, which complicates standard response assessment and is likely the reason no studies have found predictive value in enhancing tumor size or change in size. The current study examined whether contrast-enhanced T1-weighted subtraction maps (CE-ΔT1w) calculated from subtracting pre-contrast (T1) from post-contrast T1w images (T1+C) can improve quantification and predict response in GBM patients treated with bevacizumab. Methods: Recurrent GBM patients (n=160) from the BRAIN trial (AVF3708g), a multicenter Phase II trial evaluating bevacvizumab, were used in the current study. CE-ΔT1w maps were calculated 2 weeks before and 6 weeks after the first dose of bevacizumab by: 1) performing registration between T1 and T1+C images, 2) image intensity normalization of T1 and T1+C images, and 3) subtraction of T1 from T1+C images. The volume of tumor regions with positive contrast enhancement after subtraction was retained for analysis. Results: CE-ΔT1w maps greatly improved detectability of subtly enhancing lesions, particularly post-treatment. Results for PFS and OS are summarized in the table below. In all scenarios, CE-ΔT1w maps outperformed conventional tumor segmentation. Results show that size and change in size are both predictive of PFS and OS. Conclusions: CE-ΔT1w maps improve visualization and quantification of contrast enhancing tumor regions in recurrent GBM, allowing for more accurate response assessment. [Table: see text]
Vaccine therapy with tumor-specific mutated ras peptides and IL-2, GM-CSF, or both in adult patients with solid tumors.
Authors: Osama E. Rahma, Michael Hamilton, Omar Dakheel, Seth M. Steinberg, Sarah Bernstein, Jeffrey Schlom, Samir Khleif
Journal: Journal of Clinical Oncology (2012)

2577 Background: We have shown in previous trials that vaccination with mutant ras peptides corresponding to the tumor mutation is feasible and can induce specific immune responses against the mutant proteins. Immune adjuvants are used to enhance the effect of antigen vaccines. Here, we tested the ras vaccine in combination with Interleukin-2 (IL-2), GM-CSF, or the combination of both in patients with advanced malignancies. Methods: We treated 53 patients with advanced cancers (38 CRC, 11 pancreatic, 3 NSCLC and 1 cholangiocarcinoma) with 5000µg of the corresponding mutant ras peptide given SQ along with IL-2 (Arm A), GM-CSF (Arm B) or both (Arm C). IL-2 was given SQ at 6.0 million IU/m2/day starting day 5, 5 days/week for 2 weeks. GM-CSF was given SQ in a dose of 100 µg/day one day prior to each vaccination for 4 days. Vaccines were repeated every 4 weeks for a maximum of 15 cycles or until disease progression. Results: The median PFS and OS for the full cohort was 3.6, and 16.9, respectively. Median PFS was 3.9, 3.2 and 3.6 months for arm A, B, C, respectively. Median OS was 17.3, 20.8 and 9.1 months, respectively. There was no difference in PFS or OS between the three arms (p= 0.74 and 0.99, respectively). In a subgroup analysis, patients with advanced CRC had a median PFS and OS of 3.5 and 14.2 months, respectively. Most adverse events were grade I-II toxicities and resolved spontaneously. Conclusions: Two important conclusions came out of this trial: 1) no difference was found in clinical response between the three arms; and 2) although patients with CRC in the subgroup analysis progressed earlier compared to historical control (3.5 vs. 7.3 months), the time from progression to death “post progression survival, PPS” was notably longer (10.3 vs. 5.6 months). This provides further evidence to the emerging understanding of the difference in clinical trial monitoring between immunotherapy and other types of therapy. Accordingly, removing patients with standard CTEP definition of progressive disease may adversely affect the clinical outcome of vaccine therapy. We believe that future clinical trial design strategies in cancer vaccine should be modified to allow patients to continue therapy despite of disease progression.
Analysis of prognostic factors in patients with HIV-associated aggressive B-cell non-Hodgkin lymphomas.
Authors: Blessy Maria Mathew, Samir Dalia, Joseph Hall, Andrew Kuykendall, Bijal D. Shah, Celeste M. Bello, Paul A. Chervenick, Lubomir Sokol, Eduardo M. Sotomayor, Julio C. Chavez
Journal: Journal of Clinical Oncology (2014)

e19512 Background: The occurrence of non-Hodgkin lymphomas (NHLs) is a major challenge in HIV positive (HIV+) patients in the era of antiretroviral therapy (ART). Risk stratification of these patients is of paramount value. The study’s purpose was to analyze prognostic factors that could impact the survival of HIV+ patients with aggressive B-cell NHL. Methods: Patients with HIV associated aggressive B-cell NHL were identified between 1998 and 2012. Patients with indolent and primary central nervous system lymphoma were excluded. Clinical data including CD4 count, HIV viral load (VL) and opportunistic infections (OI) were analyzed using the Kaplan Meier method and statistical significance was assessed using the log-rank test. Results: A total of 55 patients were included. The male:female ratio was 7/1. Median age was 43 years (29-65). The median time from HIV to NHL diagnosis was 29 months (0 – 284). Forty four (80%) had advanced stage (III/IV). The Eastern Cooperative Oncology Group performance status was 0-1 in 62%. The most common histologies were Diffuse Large B Cell Lymphoma (DLBCL) - 33 (62%) and Burkitt’s lymphoma -18 (33%). Bulky disease was present in 6 (11%), B symptoms in 18 (33%), elevated LDH in 20 (36%), and CD4 count < 100/mL at diagnosis in 11 (20%) patients. The mean hemoglobin (Hb), serum albumin (SA) and CD4 count were 12.1 g/dL, 3.73 g/dL and 224/uL. The median CD4 count at diagnosis was 180 (5 – 680). Serum albumin < 3.7 g/dL and Hb < 10 g/dl were present in 33% and 20.5% of patients respectively. Twenty eight (51%) had ART at diagnosis. Sixty percent of patients received anthracycline based chemoimmunotherapy. The cohort’s median OS was 29 months. The OS at 5 years was 42%. Poorer OS was associated with SA< 3.7 g/dl (median OS 11 m, HR: 3.15 [CI: 1.23-8.06], p=0.017), IPI score > 3 (median OS 8 m, HR: 3.87 [CI: 1.53-9.73], p=0.003), Hb < 10 g/dl (median OS 4 m, HR: 3.72 [CI 1.43-9.63], p=0.012). The CD4 count and VL at diagnosis did not impact OS. A history of OIs had a trend toward worse OS (p=0.056). Conclusions: Anemia and hypoalbuminemia are associated with poorer OS in HIV associated aggressive B-cell NHLs and could be used as prognostic markers at NHL diagnosis in HIV+ patients. Future validation in larger studies is needed.
Entral feeding tube insertion after esophagectomy: Technique via transgastric conduit or transduodenal.
Authors: Takashi Ogata, Tetsushi Nakajima, Kazuki Kano, Yukio Maezawa, Kousuke Ikeda, Takanobu Yamada, Haruhiko Cho, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2017)

210 Background: We always used early enteral feeding after esophagectomy as perioperative management. The common procedure for feeding tube insertion is jejunostomy, but sometimes complication such as internal hernia was occurred. In case of retrosternal gastric tube reconstruction, we usually inserted feeding tube through gastric conduit. But in case of posterior mediastinal gastric tube reconstruction, this procedure was not available because of the distance between abdominal wall and gastric tube. So we have developed the new procedure for feeding tube insertion using the mobilized round ligament of liver. Methods: The aims of the study is to clarify the safety of these procedures. In case of retrosternal reconstruction, we usually inserted feeding tube from prepylorus of gastric conduit, and feeding tube was delivered through pyloric ring to 3 rd portion of duodenum(Procedure A). Insertion point of the tube was always close to abdominal wall, and easy to be guided to extra-abdomen. On the other hand, in case of posterior reconstruction, we used the new procedure as below(Procedure B). At first, the round ligament of liver was cut at the liver edge. Next, feeding tube was inserted 15~20cm from anterior wall of 2 nd portion of duodenum with Witzel suture fixation. After that, feeding tube was led to outside of the abdominal wall through in the mobilized round ligament. The cut edge of round ligament was fixed to the duodenum wall with 4-point suture at tube insertion point, and finally feeding tube completely surrounded by round ligament without direct exposure to the abdominal cavity. And to prevent internal hernia, the space between abdominal wall and mobilized round ligament was covered by omental fat. Results: From January 2012 to December 2014, 126 cases were inserted by procedure A, and from June 2015 to February 2016, 35 cases were done by procedure B. There was no trouble derived from the feeding tube insertion such as intra-operative bleeding, leakage of digestive juice, infectious complication, ileus, and there was no trouble in removal at outpatients in both procedures. Conclusions: Both procedures were safe, so we can manage the feeding tube insertion route by the reconstruction route after esophagectomy.
Absorption of a novel formulation of abiraterone acetate (AA) fine particle (AAFP) under fed and fasted conditions.
Authors: Alexander Papangelou, Anthony J. Olszanski, Cy Aaron Stein, Yuxin Zhang, Bill Bosch, Paul Nemeth
Journal: Journal of Clinical Oncology (2017)

e606 Background: AA is approved for treatment of metastatic castration-resistant prostate cancer (mCRPC). In healthy subjects administered the originator AA (OAA) formulation, AUC and C max increased by 10- and 17-fold, respectively, when administered after a high-fat meal relative to the fasted state. 1 AAFP is a proprietary formulation (utilizing SoluMatrix Fine-Particle Technology) of AA designed to improve the oral bioavailability (BA) of AA, and to potentially reduce food effects compared with the OAA formulation. In healthy subjects, AAFP 500 mg was established as bioequivalent to OAA 1000 mg in a prior study when taken in fasted conditions. Methods: Healthy male subjects (N = 25) fasted 10-h overnight before randomization in a crossover design to a single 500 mg dose of AAFP under fasted or fed (high-fat FDA breakfast 30 min before AAFP administration) conditions. There was a 7-day washout period prior to crossover; 22 subjects completed the study. Results: Drug exposure of AAFP 500 mg was significantly ( P&lt; 0.0001) greater under fed vs fasted conditions (Table). Following a single dose of AAFP 500 mg, relative BA measured by the ratio of test-to-reference geometric means of AUC and C max of abiraterone indicated that drug exposure increased under fed conditions by approximately 4.5- and 6.5-fold, respectively, vs under fasted conditions. AAFP 500 mg was safe and well-tolerated under fed or fasted conditions. Conclusions: AAFP 500 mg under fed conditions has higher BA than under fasted conditions. A direct comparative study between AAFP 500 mg and OAA 1000 mg under restricted food conditions is underway in patients with mCRPC. 1 US FDA. CDER. Abiraterone Acetate NDA 202379 Review, 2010. Clinical trial information: NCT02737332. [Table: see text]
Influence of immunohistological detection of intratumoral urokinase-type plasminogen activator (uPA) on disease outcome in endocrine-treated postmenopausal patients with hormone receptor-positive early breast cancer.
Authors: Christian F. Singer, Martin Filipits, Stephan Jahn, Luca Abete, Raimund Jakesz, Richard Greil, Thomas Bauernhofer, Werner Kwasny, Michael Seifert, Florian Fitzal, Manfred Schmitt, Farid Moinfar, Michael Gnant
Journal: Journal of Clinical Oncology (2015)

551 Background: Elevated intratumoral levels of uPA and PAI-1 in ELISA-based measurements are associated with a high recurrence risk and allow to select patients who might particularly benefit from adjuvant chemotherapy. The clinical utility of ELISA-based uPA/PAI-1 analysis is, however, greatly limited by the requirement of fresh tissue. We have therefore evaluated whether immunohistochemical uPA analysis from formalin-fixed paraffin-embedded (FFPE) tumor samples is also suited to identify women with poor clinical outcome. Methods: 547 postmenopausal patients with hormone receptor positive, early breast cancer who had received 5 years of endocrine therapy in the prospective randomized ABCSG-06 trial, and from whom FFPE tumor tissue was available, were included in this analysis. uPA protein expression was evaluated by immunohistochemistry, and was correlated with distant-disease free (DDFS) and overall survival (OS). Results: uPA protein was expressed in 296 of 547 (54%) tumors and was associated with size (p = 0.016, Chi Square test) but not with nodal status, grading, age, or receptor status. After a median follow-up of 11.5 years, patients with uPA-positive tumors experienced a significantly shorter DDFS (p = 0.005 log rank test) and OS (p = 0.022). Women with uPA-positive tumors were more likely to experience a shorter DDFS (adjusted HR for distant relapse 1.642; 95% CI 1.046-2.576; p = 0.031 Cox regression analysis) and OS (adjusted HR for death 1.348; CI 0.984-1.846; p = 0.063) than women without uPA expression. Conclusions: When measured by immunohistochemistry, intratumoral uPA protein expression predicts poor DDFS and OS in postmenopausal women with hormone receptor positive early-stage breast cancer who receive endocrine therapy. Clinical trial information: NCT00309491.
Development and validation of a prognostic nomogram and score to predict overall survival and usefulness of second-line chemotherapy in advanced pancreatic adenocarcinoma.
Authors: Angélique Vienot, Guillaume Beinse, Christophe Louvet, Louis de Mestier, Aurelia Meurisse, Francine Fein, Bruno Heyd, Denis Cleau, Christelle d'Engremont, Anne Claire Dupont-Gossard, Zaher Lakkis, Christophe Tournigand, Olivier Bouche, Benoit Rousseau, Cindy Neuzillet, Franck Bonnetain, Christophe Borg, Dewi Vernerey
Journal: Journal of Clinical Oncology (2017)

354 Background: In advanced pancreatic ductal adenocarcinoma (aPDAC), there is no consensual strategy for second-line chemotherapy (L2). Better discrimination of overall survival (OS) may help clinical decision-making in this setting. We aimed to predict OS from the beginning of L2 and to assess the benefit from chemotherapy among the identified risk groups. Methods: Analyses were derived from all consecutive aPDAC patients treated at Besancon hospital, France, during 11 years. The association of 50 parameters with OS was evaluated using univariate and multivariate Cox analyses. Based on the final model, a prognostic nomogram and score were developed, and externally validated in patients receiving L2 in three other French centers, between 2010 and 2016. Results: The development cohort included 462 patients. 395 patients (85%) were eligible for L2, of which 261 (66%) were treated. Age, smoking status, liver metastases, Eastern Cooperative Oncology Group performance status, pain, jaundice, ascites, duration of first-line chemotherapy, and type of L2 regimen were identified as independent prognostic factors for OS in L2. The final model exhibited excellent calibration and discrimination (C-index = 0.75, 95% confidence interval 0.72 to 0.78), and robust internal validity. Based on the final model, a prognostic nomogram was built. The nomogram total points were input into a prognostic score that delineated three risk groups with median OS of 11.3, 3.6 and 1.4 months (P &lt; 0.0001). By applying the score in the population eligible for L2 but untreated, the chemotherapy benefit was significant across all groups but with a magnitude of the effect decreased significantly from low to high-risk groups (P = 0.0123 for treatment and risk groups interaction term). The clinical benefit centered accuracy of the final model was confirmed by a decision curve analysis. The score ability to discriminate OS was externally confirmed in 162 patients, by identifying the same risk groups. Conclusions: These prognostic tools in patients with aPDAC can accurately predict OS before administration of L2 and strengthen the prognosis-based decision making for clinicians.
The Addition of Thalidomide in Any Line of Treatment of Multiple Myeloma, Improves Overall Survival: Single Center Experience in 246 Patients.
Authors: Eirini Katodritou, Evgenia Verrou, Anastasia Banti, Vassiliki Gastari, Dimitra Mihou, Christina Hadjiaggelidou, Dimitra Markala, Anna Lazaridou, Evangelos Terpos, Konstantinos Zervas
Journal: Blood (2007)
Analysis of overall survival (OS) based on tumor target lesion change in the phase 3 METEOR trial of cabozantinib (cabo) versus everolimus (eve) in advanced renal cell carcinoma (RCC).
Authors: Sumanta K. Pal, Robert J. Motzer, Mayer N. Fishman, Raymond S. McDermott, Jose Passos-Coelho, Evgeniy Kopyltsov, Xavier Garcia del Muro, Jesus Garcia Donas, Ramazan Yildiz, Lori Wood, Pawel Zalewski, Brian Addis Costello, Walter Michael Stadler, Timothy M Kuzel, Stephen K. Williamson, Takeyoshi Alfonso Kondo, David W Markby, Bernard Escudier, Thomas Powles, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2017)

522 Background: In the METEOR study (NCT01865747), cabo demonstrated improved progression-free survival (median 7.4 vs. 3.8 mo; HR 0.58, 95% CI 0.45–0.74; p&lt;0.0001), OS (median 21.4 vs. 16.5 mo; HR 0.66, 95% CI 0.53-0.83, p=0.0003), and objective response rate (17% vs. 3%; p&lt;0.0001) compared with eve in patients (pts) with advanced RCC who had received prior VEGFR TKI therapy (Choueiri NEJM 2015, Lancet Oncol 2016). Here we evaluate the impact of changes in target lesion size from baseline on OS. Methods: 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed per independent radiology review by CT/MRI scans at baseline, every 8 weeks for the first 12 months, and every 12 weeks thereafter. Three subgroups were defined by best change in target lesion size from baseline: decrease ≥30%, decrease &lt;30%, and any increase. Results: The rate of target lesion regression was higher in the cabo arm (75%) compared with the eve arm (48%). A higher fraction of pts had a decrease ≥30% in target lesion size in the cabo arm, while a higher fraction of pts had an increase in target lesion size in the eve arm (Table). Medians for OS with cabo were not estimable (NE) (95% CI, NE‒NE), 20.8 mo (95% CI, 18.1‒NE), and 11.1 mo (95% CI, 7.6‒15.2) for the ≥30% decrease, &lt;30% decrease, and any increase subgroups, respectively. Medians for OS with eve were NE (95% CI, 19.3‒NE), 18.0 mo (95% CI, 15.9‒20.4), and 14.0 mo (95% CI, 10.5‒16.3) for the ≥30% decrease, &lt;30% decrease, and any increase subgroups, respectively. Median duration of follow-up for OS was 18.7 mo (IQR 16.1–21.1) for cabo and 18.8 mo (16.0–21.2) for eve. A higher proportion of pts received subsequent anticancer therapy in the any increase subgroup compared with the other subgroups. Conclusions: Cabo demonstrated a higher rate of tumor target lesion regression than eve, and greater target lesion regression was associated with improved OS in pts with advanced RCC. Clinical trial information: NCT01865747. [Table: see text]
A multicenter phase III randomized double-blind placebo controlled trial of pravastatin added to first-line standard chemotherapy in patients with small cell lung cancer (SCLC).
Authors: Michael Seckl, Christian Ottensmeier, Michael H. Cullen, Peter Schmid, Lindsay E. James, Christina Wadsworth, Hannah Farrant, Dakshinamoorthy Muthukumar, Joyce Thompson, Susan Harden, Gary William Middleton, Kate Fife, Barbara Crosse, Paul Taylor, Iftekhar Khan
Journal: Journal of Clinical Oncology (2013)

7595 Background: Most SCLC patients initially respond to chemotherapy but then relapse and die so new therapies are urgently required. Pre-clinical data shows statins induce growth arrest and apoptosis in SCLC and several other tumour cell types and are additive with chemotherapy. This may in part be due to impaired Ras superfamily function as statins deplete mevalonate, reducing geranylgeranylation and farnesylation of these proteins. We therefore undertook this large pragmatic phase III trial in order to determine if overall survival (OS) was affected by the addition of pravastatin in SCLC. Methods: Patients with limited (LD) or extensive (ED) stage SCLC were randomised to pravastatin 40mg OD or placebo for up to 2 years and given standard chemotherapy according to local practice recommended as either cisplatin 60mg/m 2 iv or carboplatin AUC 5 or 6 and etoposide 120 mg/m 2 iv d1 to 3 or 100 mg BD po d2 &amp; 3; max 6 cycles plus radiotherapy as usually given. Patients were excluded if they had used statins within 12 months prior to randomisation. Stratification was: LD vs ED and ECOG 0,1 vs 2,3. Endpoints were: primary - OS; secondary - progression free survival (PFS), local PFS (local control), response rates (RR) and toxicity. Results: Between 2007 and 2012, 846 patients were randomised, 422 (49.9.%) received pravastatin and 424 (50.1%) placebo in 93 participating sites in the UK. The median age was 64 years (range 54-69); ECOG performance status: 0: 23%; 1: 54%; 2: 17% and 3: 6%; weight 72.6 kg; LD, 357 (42.2%); ED, 479 (56.6%); 211 (24.9%) had ipsilateral effusion and 201 (23.8%) had ipsilateral SCF lymph nodes; Relative Dose intensity of cisplatin/carboplatin and etoposide was 91.6% (range 80.8 to 99.7), and 94.7% (range 85.7 to 100); 83.4% vs 86.3% completed &gt; 4 cycles of chemotherapy on the pravastatin and placebo arms respectively. Most patients completed 6 cycles of chemotherapy: 263 (62.3%) vs 265 (62.5%) in the pravastatin vs. placebo groups. Updated results showing OS, PFS, local PFS and toxicity will be presented. Conclusions: This trial will report on whether pravastatin 40 mg OD added to standard therapy alters the outcome for SCLC patients. Clinical trial information: ISRCTN56306957.