tbuckley/cabot-search huggingface dataset:
Retrospective analysis of CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) treated with chemotherapy with or without rituximab
Authors: K. Miyazaki, M. Yamaguchi, R. Suzuki, N. Niitsu, D. Ennishi, J. Tamaru, Y. Kagami, N. Katayama, T. Kinoshita, S. Nakamura
Journal: Journal of Clinical Oncology (2009)

8551 Background: CD5+ DLBCL comprises 5–10% of DLBCL, and shows a high incidence of central nervous system (CNS) relapse. It has been included in the 4th WHO classification as an immunohistochemical subgroup. To clarify the prognosis and incidence of CNS relapse of CD5+ DLBCL in the rituximab-era, we conducted a multicenter retrospective study. Methods: We analyzed 313 patients (pts) with CD5+ DLBCL who received chemotherapy with (n=164) or without rituximab (n=149). The current series includes 107 out of 120 pts described in our previous study (Haematologica, 2008). Intravascular large B-cell lymphoma, primary CNS DLBCL, and secondary CD5+ DLBCL were excluded from the study population. Results: 313 pts showed the following clinical features: median age, 67 (range: 15–93); M:F=163:150; elevated serum LDH level, 71%; stage III/IV, 64%; IPI HI/H, 53%. No significant difference in clinical background such as the IPI and its five components, B symptom, male sex, and bone marrow involvement was found between pts who were treated with and without rituximab. Pts treated without rituximab received more dose-intensive chemotherapies (CHOP14, third-generation regimen, and high dose cytarabine-based regimen) than those treated with rituximab (24% vs. 7%, P&lt;0.0001). The CR rate was higher in pts received rituximab than those without (81% vs. 65%; P=0.0014). The median follow-up was 28 months in pts who received rituximab (range: 7–77) and 68 months in those who did not (range: 6–187). Overall survival (OS) was significantly superior for pts with rituximab than for those without (2-yr OS: 68% vs. 54%, P=0.003). Multivariate analysis revealed that the use of rituximab was favorably associated with OS (HR=1.81, 95% CI: 1.26–2.58, P=0.001), but dose-intensive chemotherapies did not affect OS. However, the incidence of CNS relapse was not different between the two groups (2-yr CNS relapse rate: 11.9% vs. 11.4%, P=0.91). 16 of the 20 pts (80%) with CNS relapse in the rituximab group had brain parenchymal disease. Conclusions: Our data show that rituximab improves OS of pts with CD5+ DLBCL, but does not prevent CNS relapse. Future prospective studies to decrease CNS disease for CD5+ DLBCL are warranted. No significant financial relationships to disclose.
Clinical Trials of Therapeutics for the Prevention of Congenital Zika Virus Disease: Challenges and Potential Solutions
Authors: Alex P. Salam, Amanda Rojek, Jake Dunning, Peter W. Horby
Journal: Annals of Internal Medicine (2017)

Zika virus (ZIKV) infection in pregnancy is associated with adverse fetal outcomes, such as microcephaly and other congenital malformations. No therapeutic options are available to pregnant women with ZIKV infection to prevent these effects. Drug trials in pregnancy raise several scientific, ethical, and logistic challenges, which are compounded further in ZIKV because of limited knowledge of the disease pathophysiology and a product development pipeline in its infancy. We evaluate the major challenges in choosing therapeutics to prevent congenital ZIKV disease and conducting clinical trials of these treatments, with a focus on preventing congenital central nervous system malformations. These challenges must be characterized and planned for now so that clinical trials can progress expediently and effectively in the future.
First stage results of a phase II trial of sorafenib plus doxorubicin (SD) in patients (pts) with advanced hepatocellular carcinoma (HCC) who progressed (POD) on sorafenib (S).
Authors: Ghassan K. Abou-Alfa, Marinela Capanu, Richard Kinh Gian Do, Ellen Hollywood, Michele Ly, Joanne F. Chou, Jean Kyung Lee, Louise Catherine Connell, Peter Justin Wan, Margaret Bradley, James J. Harding, Leonard Saltz
Journal: Journal of Clinical Oncology (2015)

e15147 Background: Retrospective analysis of 14 pts with advanced HCC treated with SD after POD on S, showed a median progression free survival (PFS) and overall survival (OS) of 3.4 and 10.1 months respectively. We theorize SD may have synergistic activity in HCC through inhibition of Raf-1 by S promoting D induced ASK-1 mediated apoptosis. Methods: A single arm phase II study evaluated SD in pts with advanced HCC with RECIST 1.1 radiologic POD on S, ECOG 0-1, Child-Pugh A, and adequate bone marrow, renal, hepatic and cardiac function. The primary endpoint was OS at 6 months (OS6). Statistical plan: two stage design, unacceptable OS6 50%, acceptable OS6 72%, type I and II errors 5 and15% respectively. Secondary endpoints: median PFS, median OS, tolerance to SD, response rate by RECIST 1.1, and associations between previous length of exposure to S and OS and PFS. Results: Starting April 2012, 15 pts were enrolled. Male = 13, Median age 70 years (range 24-82), Median KPS 80%. The median duration of prior S was 3.5 months (1.3-27.7). The median cumulative D dose was 285mg/m2 (60-360 mg/m2), and median dose of S 400mg (200-800mg). OS6 was 87% (95% CI 56% to 96%), with median PFS, and OS of 4.1 months (95% CI 1.6-8.6), and 16.5 months (95% CI 6.3- not reached) respectively. Neither OS nor PFS were associated with previous sorafenib duration (p value 0.8 and 0.4 respectively). There were 1 (6%) partial response and 12 stable disease (80%) of whom 5 (42%) has SD for ≥ 4 months. Grade 3 and 4 adverse events ≥ 10% of the pts were: neutropenia (46%), lymphopenia (67%), hyperbilirubinemia (13%), anemia (20%), elevated AST (27%) and ALT (20%), ascites (13%), GI bleed (13%), hypophosphatemia (20%), hyponatremia (27%), and hypertension (20%). There were no treatment related deaths. Conclusions: With OS6 of 87%, the first stage decision rule requiring 8 out of 15 pts to be alive at 6 months has been met. The study is completing accrual of its second stage for a total of 30 pts. Reported adverse events are similar to those reported in the literature. Pre- and post-treatment ASK-1 and pERK expression levels in biopsied tumor tissue samples were obtained and will be assessed and presented at a later time. Clinical trial information: NCT01840592.
Bevacizumab (BV) plus chemotherapy (CT) as first-line treatment of patients with metastatic colorectal cancer (mCRC): First results from a large community-based observational cohort study in Germany
Authors: D. Arnold, M. Kindler, V. Petersen, D. Tummes, M. Moelle, C. Schoeberl, S. Srock, A. Kutscheidt, W. Grothe
Journal: Journal of Clinical Oncology (2009)

e15057 Background: BV prolongs overall survival (OS) and progression-free survival (PFS) when added to standard CT for patients (pts) with mCRC. After approval of BV in Germany in 01/05, this observational cohort study was initiated in pts receiving BV with various first-line CT regimens to evaluate safety events and effectiveness. Methods: To facilitate and evaluate enrollment of a typical mCRC population, eligibility criteria were minimized. Choice of the CT regimen was at physician´s discretion, but influenced by the current registration status. Predefined endpoints were treatment characteristics, response rate (RR), PFS, OS, and adverse events assessed as potentially related to the treatment (AERT) or as severe (SAE). Pts are followed for up to 4 years, and clinical data were updated every cycle (2–4 weeks). Results: 1,300 pts were enrolled at 261 sites from 01/05 through 06/08; abstract data cutoff date was 11/24/08. Median age: 64 (range 19–100) years, &gt; 70 years.: 25%; male 63%; ECOG PS status 0–1/2/&gt;2 88%/11%/1%. CT choice was fluoropyrimidine (FU)/BV alone (any 5-FU or capecitabine) 12%; FU/BV/oxaliplatin 18%; FU/BV/irinotecan 69%; other 1%. Median treatment duration with BV was 7.4 (range 0–28) months; duration &gt; 10 months 21%. 60-day mortality was 4.0%. In total, 183 AERT were reported in 10% of pts., most commonly diarrhea (34 AERT), nausea (26) and hypertension (18). Reported SAE were deep venous TE in 0.8% of pts, bleeding 1.2%, pulmonary embolism 0.5%, arterial TE 0.4%. Best investigator- assessed RR was 59% (CR 10%, PR 49%; all pts) with 64% for FU/BV/oxaliplatin, 59% for FU/BV/irinotecan and 53% for FU/BV alone. Conclusions: The safety profile of BV in this population of mCRC pts with different CT regimens appears consistent with that observed in the other reports like BRiTE or first BEATrial. RR in this preliminary dataset are higher than that reported in the randomized controlled trials, but likely biased by the methodology of evaluation. However, activity with FU/BV alone was surprisingly high. Updated efficacy data including PFS will be presented. [Table: see text]
A comparison of surrogate endpoints for all cause mortality in men with localized unfavorable-risk prostate cancer.
Authors: Trevor Joseph Royce, Ming-Hui Chen, Jing Wu, Marian Loffredo, Andrew A. Renshaw, Philip W. Kantoff, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2017)

21 Background: Several surrogates for prostate cancer-specific mortality exist, but whether these are surrogates for all cause mortality (ACM), and how their performance compares, is unknown. We investigated the relative efficacy of 4 candidate surrogates for ACM using the proportion of treatment effect (PTE) metric. Methods: Two-hundred and six men with localized unfavorable-risk prostate cancer were randomized to radiation therapy (RT) or RT and 6 months of androgen-deprivation therapy (ADT) from 1995 to 2001 and followed for a median of 16.62 years. Among the 159 men with no or minimal comorbidity, a significant reduction in the risk of death was observed in those randomized to RT and ADT versus RT alone; these 159 men formed the study cohort. In order to assess whether the candidate surrogated satisfied Prentice’s criteria for surrogacy, Cox regression analyses were performed to assess the risk of death for each of the candidate surrogates and treatment before and after adjusting for prostate-specific antigen (PSA), age at randomization, T category, and Gleason score. Results: PSA nadir &gt; 0.5 ng/mL, PSA doubling time &lt; 9 months and interval to PSA failure &lt; 30 months met Prentice’s criteria for surrogacy (P = 0.01, 0.003, and 0.03 for the surrogate covariate in the multivariable model, respectively) for ACM, while PSA failure did not (P = 0.10). For the three surrogates, the PTE values were 103.86%, 43.09%, and 41.26%, respectively. Conclusions: A PSA nadir value of &gt; 0.5 ng/mL following RT and ADT identified men prior to PSA failure who were at high-risk for death and therefore could be used to select men for entry, at the time of PSA nadir and before PSA failure, onto randomized trials evaluating the impact on survival of salvage ADT with or without agents shown to prolong survival in men with castrate-resistant metastatic prostate cancer. By enriching study cohorts with men who have achieved a surrogate endpoint for ACM, one can enhance the likelihood that the study will be able to observe whether survival is prolonged when novel treatment is added to ADT, as compared to ADT alone, in an abbreviated time period. Clinical Trial Number: NCT00116220
Do Patterns of Breast Cancer Surgical Care Reflect National Voting Records?
Authors: Lisa A. Newman
Journal: JAMA Surgery (2017)

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Oncologists' and primary care providers' awareness of late effects of cancer treatment: Implications for survivorship care.
Authors: Larissa Nekhlyudov, Noreen Aziz, Catherine C. Lerro, Katherine S. Virgo
Journal: Journal of Clinical Oncology (2012)

6008 Background: There is a growing population of cancer survivors, many of whom may experience late or long-term effects (LEs) of treatment. The goal of our study was to describe and compare primary care providers’ (PCP) and oncologists’ awareness of LEs. Methods: The Survey of Physician Attitudes Regarding the Care of Cancer Survivors was completed by a nationally representative sample of 1,072 PCPs and 1,130 oncologists (cooperation rate 65%). Respondents were asked to report for each of four standard chemotherapy drugs used to treat breast or colorectal cancer the five LEs they had observed and/or had seen reported in the literature. We described and compared the physicians’ responses and, using separate multinomial logistic regression models, determined predictors of their ability to identify the main LEs for all agents, adjusting for physician demographics and practice characteristics. Results: Almost all (95.3%) oncologists identified cardiac dysfunction as a LE of doxorubicin (Adriamycin), and peripheral neuropathy as LEs of both taxol (97.3%) and oxaliplatin (96.6%); while these LEs were identified by only 55.1%, 21.8% and 21.8% of PCPs, respectively. Most oncologists identified premature menopause (71.4%) and secondary malignancies (62.0%) as LEs of cytoxan, compared with only 14.8% and 17.2% of PCPs. Main LEs for all four chemotherapy drugs were identified by 65% (n=741) of oncologists and only 6% (n=60) of PCPs. In adjusted models, oncologists were more likely to identify the main LEs for all chemotherapy drugs if they spent 51-90% (OR 1.87, 95% CI 1.21-2.88) or &gt;90% (OR 1.82, 95% CI 1.08-3.08) of their time on patient care, and less likely if they were not board certified (OR 0.58, 95% CI 0.37-0.89). African American PCPs were less likely to identify the main LEs for all chemotherapy drugs (OR 0.19, 95% CI 0.08-0.45). Conclusions: Oncologists often identified the main LEs of cancer drugs while PCPs did not. While not surprising, these findings emphasize that in the transition of patients from oncology to primary care settings, PCPs should be informed about the LEs of cancer treatment so that they may be better prepared to recognize and address these among survivors in their post-treatment care.
A pemetrexed-based genetic study of Chinese Han patients with advanced non-small cell lung cancer (NSCLC).
Authors: Shun Lu, Xiaomin Niu, Ziming Li, Yongfeng Yu, Xiangyun Ye, Yun Liu, Zhiwei Chen, Mengyuan Kan
Journal: Journal of Clinical Oncology (2013)

e19014 Background: Pemetrexed has been approved for ﬁrst- and second-line treatment in patients with non-small cell lung cancer (NSCLC). Two studies have confirmed the role of polymorphisms (SNPs) in reduced folate carrier (SLC19A1) is related with the survival differences in pemetrexed-treated NSCLC in Caucasian population. Considering different genetic backgrounds in different populations, our study was aimed to identify candidate SNPs for pemetrexed-treated NSCLC in Chinese Han population. Methods: Fifty-seven patients with previously treated NSCLC received pemetrexed-based third-line treatment from Shanghai Chest Hospital from Nov 2006 to Jul 2011. Four genes, SLC19A1, gamma-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase (MTR), responsible for pemetrexed transport and activation were evaluated. The five SNPs (rs4819128, rs914232, rs4818789, rs3788189, rs1051298) in SLC19A1, two SNPs (rs3780130, rs3780126) in GGH, two SNPs (rs1801133, rs180131) in MTHER, and one SNP (rs1805087) in MTR were selected based on the HapMap Chinese Han databases. All SNP genotyping was performed by TaqMan PCR using the ABI Prism 7900HT Sequence Detection System. Kaplan-Meier cumulative probability and Cox multivariate analyses were used to evaluate the relationship between genetic variations with survival outcome. Results: Fifty-seven patients received a median of three cycles (range, 1-16 cycles) of pemetrexed-based treatment. Median overall survival (OS) and progression-free survival (PFS) times were 23.0 and 3.2 months, respectively. Patients with AA/AG genotype of SLC19A1 rs1051298 had the better PFS and OS compared with GG genotype (5.5m vs 1.9m for PFS, P=0.047; 45.5m vs 17m for OS, P=0.001). The TT/TA genotype of novel GGH rs3780130 was correlated with better PFS compared with AA genotype (5.8m vs 2.5m, P=0.029). Conclusions: This study in Chinese Han NSCLC patients identified the unique result that novel TT/TA genotype of GGH rs3780130 was related with better PFS for pemetrexed-based treatment. Meanwhile, we obtained the same result with that in Caucasian study, AA/AG genotype of SLC19A1 rs1051298 was related with better PFS and OS.
Occupational respiratory allergy in peach crop workers
Authors: R. Pérez‐Calderón, M. Á. Gonzalo‐Garijo, F. J. Rodríguez‐Velasco, S. Sánchez‐Vega, B. Bartolomé‐Zavala
Journal: Allergy (2017)

Occupational respiratory diseases in workers of peach tree crops have been reported punctually and have been associated with sensitization to proteins present in both pollen and leaf tree. We report the study of 37 workers with respiratory symptoms related to occupational exposure to peach trees.Prick tests and specific IgE determinations were performed with extracts from leaves and branches of peach tree. Immunodetection in leaf extract was realized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis SDS-PAGE-immunoblotting with patient sera and rabbit serum anti-Pru p 3. Immunodetection inhibition was performed with rPru p 3 and pollen profilins. The clinical relevance of sensitization was demonstrated by specific bronchial challenge test (SBCT) with peach leaf extract.Most patients suffered symptoms when peach trees had leaves, specifically during thinning and harvesting fruit (rhinoconjunctivitis: 100% and asthma: 67.5%). Sensitization to leaf extract was demonstrated in 86% of patients. IgE-immunoblotting with peach leaf extract revealed in six patient sera a pair of bands of 10 and 16 kDa, and in nine a 16-kDa band. Those bands could be two isoforms of peach leaf lipid transfer proteins( LTP), so the recognition frequency of some LTP isoform by our patient sera was 42%. 33% of the sera recognized a doubled band of about 14.5 kDa and this recognition was inhibited by nPho d 2. The SBCT with peach leaf extract was positive in the asthmatic sensitized patients tested.Sensitization to peach leaves was the cause of occupational respiratory symptoms in our patients. Some patient sera revealed IgE-binding proteins matching LTP and/or profilin.
Elderly advanced non-small-cell lung cancer (NSCLC) patients (p) treated with vinorelbine (vrb) plus gemcitabine (gem): Molecular correlates
Authors: I. Maestu, D. Isla, P. Diz, J. Muñoz, S. Oramas, R. García, M. Provencio, A. Jaen, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2006)

17043 Background: The clinical benefit of non-cisplatin doublets (vrb/gem) vs a single agent (vrb or gem) in elderly p is still controversial. The present study focuses on clinical outcome with vrb/gem in the elderly and the role of functional status. Genetic predictive markers of response to vrb/gem will also be examined in genomic and cDNA from tumor and circulating tumor DNA. Methods: NSCLC p with stage IIIB (pleural effusion or supraclavicular lymph nodes)-IV or recurrent disease and age ≥ 70 years were treated with vrb (25 mg/m 2 iv or 60–80 mg/m 2 oral) plus gem 1200 mg/m 2 , days 1,8 every 21 days. Activities of daily living (ADL), instrumental activities of dalily living (IADL) and comorbidities were evaluated. Primary tumor and baseline serum DNA were collected for assessment of microtubule associated protein 4 (MAP4) in tumor and checkpoint with forkhead-associated and ring finger (CHFR) methylation in serum. A preliminary analysis of response and toxicity was performed on 51 p. Results: From April 2004 to December 2005, 145 p were included. Data on 68 p is available: median age 74.5 years (70–83); stage IIIB: 21.2%, IV: 78.7%; PS 0: 23.4%, 1: 54.6%, 2: 21.8%. Self-sufficiency in ADL and IADL was 56.2% and 25% of the p analyzed. All p but 8 had comorbidities. Response rate for 51 p: partial response, 12% (95% CI, 8.9–20%); stable disease, 32% (95% CI, 19.2–44.8%). Main hematological toxicities: grade 3/4 neutropenia, 8.3/4.1%; grade 3 thrombocytopenia, 4.1%; grade 3 anemia, 4.1% of the p respectively. Conclusions: Preliminary findings indicate that vrb/gem is feasible in elderly p with acceptable toxicity. Complete data on response, survival and genetic markers will be presented. No significant financial relationships to disclose.
Randomized phase II trial of abiraterone +/- dasatinib for patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Tanya B. Dorff, David I. Quinn, Jacek K. Pinski, Amir Goldkorn, Sarmad Sadeghi, Denice Tsao-Wei, Susan G. Groshen, Peter Kuhn, Mitchell E. Gross
Journal: Journal of Clinical Oncology (2017)

167 Background: Signaling via Src pathway is thought to be a mediator of resistance to androgen targeted therapy in mCRPC. We sought to determine whether adding the Src inhibitor dasatinib (Das) to abiraterone (Abi) would prolong progression free survival (PFS). Methods: Eligible patients had mCRPC which had progressed on androgen targeted therapies but no prior chemotherapy. Abi was prescribed at 1000 mg daily with prednisone 5 mg BID (both arms) and Das 100 mg daily added for Arm B. Primary endpoint was PFS at 24 weeks. Interim analysis planned after 48 subjects randomized but study terminated early due to lack of funding. PFS was evaluated using logrank testing and responses were compared using Fisher’s exact test. Circulating tumor cells (CTC) were evaluated with EPIC platform. Results: 26 men were randomized, 14 to Abi+Das and 12 to Abi. Median age was 67 (56-85), baseline PSA 19.8 (0.84-1387). Only 1 patient had received ketoconazole, none had received enzalutamide. With 30 months median follow-up, median PFS was 15.7 (95% CI:8.2, 31.1+) months for Abi+Das and 9 (95% CI: 4.4, 45.6+) months for Abi (p = 0.30). 86% were progression free at 24 weeks with Abi+Das compared to 75% on Abi. RECIST responses were seen in 5/14 (35%, 95% CI: 17%, 66%) with 2 CR on Abi+Das and 1/12 (8%, 95% CI (0%, 37%) on Abi (p = 0.16). With a specificity of 83%, the probability that the true rate of CR in intervention arm is higher or doubled (ex: 35% vs 17%) is 71%. Grade &gt; 3 toxicities more common on Das arm included hypertension (43% vs 8% Abi), pleural effusion/dyspnea (14% vs 0 Abi), and gastrointestinal (25% vs 8%). CTC were detected at baseline in 8/17 evaluable patients (3/8 Abi, 5/9 Abi+Das), median 2.7 CTC/mL blood (range 0.5-59.7) At week 4, CTC increased in 1/8 (12.5%) on Abi vs 4/9 (44.4%) on Abi+Das but by week 12 CTC increases persisted in 2/8 (25%) on Abi and 1/9 (11%) on Abi+Das. Conclusions: Das did not significantly prolong PFS in combination with Abi although power was limited due to incomplete study cohort. Abi+Das was associated with robust objective responses including RECIST CR. Clinical trial information: NCT01685125.