tbuckley/cabot-search huggingface dataset:
Rituximab hypersensitivity reactions (HSR): Predictors of recurrent and severe reactions based on severity of reaction, NHL histologic subtype, and burden of disease.
Authors: David A Sallman, Eric Macklin, Shihab Ali, James Michaelson, Jeffrey A. Barnes, Jeremy S. Abramson, Aleena Banerji, Ephraim P. Hochberg
Journal: Journal of Clinical Oncology (2012)

e18520 Background: Rituximab is an anti-CD20 monoclonal antibody with efficacy in B-cell malignancies. Grade II-IV HSR occur in 5-10% of patients. There are no data to predict which patients are at risk for more severe rituximab HSR as well as no data on eventual successful rituximab administration in this population. Methods: We analyzed all rituximab HSR in patients at Massachusetts General Hospital between 2006-2010. Patients included had documented HSR on the chemotherapy infusion sheet on our electronic medical record or via referral to allergy for desensitization. Control rituximab-treated patients were identified from tumor registry data. ICD3 codes were used to determine the histologic subtypes. Rates of HSR were analyzed by logistic regression and Fisher's exact test. Severity of HSR was based on an established classification system. Results: Immediate HSR occurred in 9% of patients (79/901) treated with rituximab and premedications. A majority of patients with a HSR developed symptoms on their initial infusion (76%); however, 46% of moderate or severe HSR occurred on subsequent infusions. Severity of HSR was directly correlated to the risk of a recurrent reaction where all patients with severe HSRs and 56% of patients with moderate HSRs had a recurrent reaction in contrast to only 36% of patients with mild reactions (p = 0.005). Advanced stage of disease increased the risk of a moderate or severe HSR (HR = 4, p = 0.02). Waldenstrom’s Macroglobulinemia (WM) accounted for 10% of all HSR while representing only 1% of rituximab treated pts (p &lt; .003 adjusting for multiple comparisons) and 70% of these patients had a HSR. All patients with complex HSR who were referred to allergy for desensitization (n=14) were able to complete therapy safely. Conclusions: Severe rituximab HSR commonly occurs after the initial infusion. Severity of the HSR predicted recurrent HSR and an advanced stage of disease predicted more severe reactions. WM had a disproportionately higher risk for HSR. Despite HSR, we found that all patients were able to tolerate the recommended number of infusions without severe adverse events utilizing medical management and/or desensitization.
Early data of phase III study in patients (pts) with stage IV non-small-cell lung cancer (NSCLC) treated with two cycles of cisplatin/gemcitabine followed by a randomization to three additional cycles of the same combination or gemcitabine alone
Authors: S. Novello, C. Barone, R. Buosi, G. Michetti, S. Barbera, M. Fioretti, A. Masotti, L. Garetto, P. Bruzzi, G. V. Scagliotti
Journal: Journal of Clinical Oncology (2004)

7069 Background: In stage IV NSCLC platinum-based chemotherapy confers survival advantage and produces symptom relief but the real benefit remains small and sometime it is outweighed by toxicity. Available data do not support the use of chemotherapy beyond 3–4 cycles of therapy and the best response is usually reported after 2–3 cycles of chemotherapy. Methods We report the preliminary results of a multi-center, phase III comparison in which chemonaive, stage IV pts with measurable disease after two cycles of cisplatin (75 mg/m2 d2) plus gemcitabine (1250 mg/m2 d1,8) every 21 days, were randomized (in case of Complete Response,Partial Response or Stable Disease) to receive three additional courses of the same combination (arm A) or gemcitabine alone at the same dose and schedule (arm B). Primary objective of the study was the no-inferiority of arm B in terms of 1-year and median survival time using an hazard ratio of 0.75 (one sided alpha error=5%, power = 80%) Results: Between Jan. 2001 and Dec. 2003 we enrolled 294 pts and 207 randomized. Median age was 62 years (range 35–76), 78.5% male, PS 0/1 93.5%, adenocarcinoma 55%, 13% with asymptomatic brain mts. Toxicity data were as follows: Response rate after 2 cycles was76/262 (29%), 49% SD, 12% PD and 10% NE. Among the randomized the best overall objective response was 42/85 (49%) in arm A and 35/101 (34%) in arm B. As December 2003, 99 patients died and 150 progressed. Mature survival data will be presented at the time of the meeting. Conclusions: Early data indicate equivalent activity in terms of response rate but lower toxicity in arm B. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly National Research Council
Weekly paclitaxel (wPCT) for pretreated patients (pts) with advanced non-small cell lung cancer (aNSCLC): Updated data from a single institution experience in the daily clinical practice.
Authors: Mariachiara Dipasquale, Orazio Caffo, Viviana Murgia, Antonello Veccia, Sonia Brugnara, Alessia Caldara, Antonella Ferro, Michela Frisinghelli, Francesca Maines, Lucianna Russo, Barbara Soini, Francesco Valduga, Enzo Galligioni
Journal: Journal of Clinical Oncology (2014)

e19143 Background: Pemetrexed and docetaxel represent the reference treatments as second line chemotherapy for pts with aNSCLC after failure of a platinum-based treatment, with a response rate (RR) < 10%. However, non-squamous aNSCLC pts could have received pemetrexed into the first line setting and docetaxel may present a relevant side effects burden, in both 3-week and weekly schedules. wPCT is a well tolerated drug which proved to be active in aNSCLC. In the attempt to improve pts compliance we have adopted wPCT in the daily practice and presented a preliminary analysis at WLCL 2013. The updated and final analysis of this experience is the aim of this presentation. Methods: From January 2010 to October 2013, all pts with aNSCLC progressing after platinum-based chemotherapy and eligible for further chemotherapy, received wPCT at 80 mg/sqm for 6 consecutive weeks, followed by a 2-week rest. In absence of clinical evidence of progressive disease at least two courses of wPCT were planned before instrumental re-staging. Responders pts continued the treatment up to a maximum of 4 courses. Results: A consecutive series of 60 pts was treated in our institution with wPCT. The median age was 61.5 yrs (range 32-74). Fifty, 5, and 5 pts respectively received wPCT as second, third and fourth line treatment. Twelve pts received only 1 wPCT course, 38 pts 2 courses, 4 pts 3 courses, and 6 pts 4 courses, for a total number of 124 administered courses. wPCT was well tolerated: 1 pt experienced a grade 4 anemia, and 3 more pts experienced a grade 3 toxicity (1 pt thrombocytopenia, 1 pt liver and 1 pt diarrhea). No toxicity-related treatment interruptions were recorded. Eleven pts (21%) achieved a partial response and 10 (17%) a stable disease. After a median follow-up of 6.5 mos, the median PFS and OS were 4 and 9 mos, respectively. The 1-y OS was 29.9%. Conclusions: In our experience wPCT may represent a reasonable chemotherapeutic option in daily clinical practice for pre-treated aNSCLC pts, with a manageable toxicity profile, and may provide disease control rates comparable to those of docetaxel and pemetrexed.
Cell cycle progression score to modify treatment decisions in prostate cancer: Results of an ongoing registry trial.
Authors: E. David Crawford, Ashok J. Kar, Mark C. Scholz, Jeffrey E. Fegan, Rajesh R. Kaldate, Michael K. Brawer
Journal: Journal of Clinical Oncology (2014)

e16055 Background: Improved prognostic markers that provide individual patient risk stratification are a pressing need in prostate cancer. The cell cycle progression (CCP) test (Prolaris, Myriad Genetic Laboratories, Inc.) is a novel prognostic assay that has been validated in multiple cohorts and provides accurate risk of prostate cancer-specific disease progression and disease specific mortality risk when combined with standard clinicopathologic parameters. This study evaluated clinicians’ judgment regarding the clinical utility of the CCP test in a prospective registry. Methods: Clinicians ordering the CCP test commercially were asked to complete a survey regarding their treatment recommendations before and after they received the CCP test result. In addition, clinicians were asked how influential the CCP test result was in making therapeutic decisions on a five point scale (0=none, 4=very high). Results: Currently, 331 patients have been enrolled and 150 clinicians have completed surveys on the influence of the CCP signature test in 305 cases. In 26 additional surveys, the therapeutic decision was undecided pre-test. In 65% of cases, there was a change recorded between the therapy initially planned and the therapy actually selected. The table shows the change in intended therapeutic burden from pre-CCP test to post-CCP test. In 122 of 305 (40%) cases, clinicians indicated they would reduce the intended therapeutic burden post-CCP test. The CCP test influenced treatment selection to a ‘high’ or ‘very high’ degree in 54.9% cases and had “low” or “no” influence in only 12.4% of cases. Conclusions: Based on the judgment of ordering physicians, the CCP score appears to add meaningful new information to risk assessment for localized prostate cancer patients. Test results led to major changes in treatment decisions with a significant increase in conservative management options, including active surveillance or watchful waiting. Change in intended therapeutic options (Pre-CCP test to post-CCP test) Total (n=305) Reduction 122 (40.0%) No change 107 (35.1%) Increase 76 (24.9%)
Cardiovascular Gene Therapy: Past, Present, and Future
Authors: Seppo Ylä-Herttuala, Andrew H. Baker
Journal: Molecular Therapy (2017)

Cardiovascular diseases remain a large global health problem. Although several conventional small-molecule treatments are available for common cardiovascular problems, gene therapy is a potential treatment option for acquired and inherited cardiovascular diseases that remain with unmet clinical needs. Among potential targets for gene therapy are severe cardiac and peripheral ischemia, heart failure, vein graft failure, and some forms of dyslipidemias. The first approved gene therapy in the Western world was indicated for lipoprotein lipase deficiency, which causes high plasma triglyceride levels. With improved gene delivery methods and more efficient vectors, together with interventional transgene strategies aligned for a better understanding of the pathophysiology of these diseases, new approaches are currently tested for safety and efficacy in clinical trials. In this article, we integrate a historical perspective with recent advances that will likely affect clinical development in this research area.
Survival by pattern of tumor progression during prior sorafenib (SOR) treatment in patients with hepatocellular carcinoma (HCC) in the phase III RESORCE trial comparing second-line treatment with regorafenib (REG) or placebo.
Authors: Jordi Bruix, Philippe Merle, Alessandro Granito, Yi-Hsiang Huang, Gyorgy Bodoky, Marc Pracht, Osamu Yokosuka, René Gerolami, Gianluca Masi, Paul J. Ross, Shukui Qin, Tianqiang Song, Jean-Pierre Bronowicki, Isabelle Ollivier-Hourmand, Masatoshi Kudo, Marie-Aude Le Berre, Gerold Meinhardt, Guohong Han
Journal: Journal of Clinical Oncology (2017)

229 Background: HCC progression may be due to tumor growth or new intrahepatic or extrahepatic lesions. RECIST does not discriminate between progression patterns even though the prognosis may differ (Reig, Hepatology 2013). REG improves overall survival (OS) in patients with HCC who progress during SOR treatment (HR 0.63; 95% CI 0.50, 0.79; P &lt; 0.001). This exploratory analysis aimed to validate the pattern of progression concept in a global cohort treated with prior SOR and to assess the impact of REG on survival by prior progression. Methods: Adults with HCC who tolerated SOR and had radiologic progression during SOR, Child–Pugh A liver function, and ECOG PS 0–1 were randomized 2:1 to REG 160 mg/day or placebo during weeks 1–3 of each 4-week cycle. Progression during SOR was due to tumor growth or new lesions. Post-progression survival (PPS) was the time from progression on SOR until death. Results: Baseline characteristics of the 573 randomized patients (REG = 379; placebo = 194) were balanced; median age was 63 years, 88% were male, 87% were BCLC stage C, 29% had macrovascular invasion, and 72% had extrahepatic disease. Hazard ratios favored REG irrespective of pattern of progression during prior SOR, but differed according to progression pattern (Table). Conclusions: The development of new extrahepatic lesions is associated with worse survival irrespective of treatment. REG provided an OS benefit, regardless of progression pattern. Progression pattern may be a key prognostic parameter and should be considered in future trial design and analysis. Clinical trial information: NCT01774344. [Table: see text]
ICU-acquired candidaemia in France: Epidemiology and temporal trends, 2004–2013 – A study from the REA-RAISIN network
Authors: Olivier Baldesi, Sébastien Bailly, Stéphane Ruckly, Alain Lepape, François L'Heriteau, Martine Aupee, Sandrine Boussat, Caroline Bervas, Anais Machut, Anne Berger-Carbonne, Anne Savey, Jean François Timsit
Journal: Journal of Infection (2017)
Rapid, ultra-low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Daniel H. Hovelson, Chia-Jen Liu, Yugang Wang, Qing Kang, Christine Haakenson, John Langmore, Emmanuel Kamberov, Nithya Ramnath, John C. Krauss, Moshe Talpaz, Rashmi Chugh, David Hyland, Missy Tuck, Kirk Herman, Hatim Husain, Muneesh Tewari, Arul M. Chinnaiyan, Ryan Mills, Todd Matthew Morgan, Scott A. Tomlins
Journal: Journal of Clinical Oncology (2017)

144 Background: Although cell free DNA (cfDNA) profiling by next generation sequencing (NGS) holds great promise for precision oncology, the inability to estimate tumor content a priori typically results in ultra-deep sequencing (e.g. 10,000x) based approaches—often at limited loci—to ensure accurate assessment of cfDNA samples where tumor content can be &lt; 0.1%. However, a large subset of patients with advanced cancers, where most precision oncology is applied, have much greater cfDNA tumor content. Methods: Here we demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) on benchtop sequencers as a precision medicine screening strategy based on ultra-low coverage (~0.005x) tumor content determination through genome-wide copy number alteration (CNA) profiling using 48 plasma cfDNA samples from patients with advanced cancer. Results: Using this approach, we identified therapeutically relevant focal CNAs in 13 of 48 (27%) cfDNA samples from patients with metastatic cancer, including 11 of 36 (31%) from patients with mCRPC. We further show that PRINCe is effective at whole genome coverages as low as 0.005x. Combining PRINCe with targeted multiplexed-PCR NGS of the same cfDNA enables mutation and CNA assessment using effective coverage as low as 25x based on calibrating sequencing depth to cfDNA tumor content. Lastly, PRINCe identifies pre-treatment cfDNA copy number profiles that can be used for inexpensive disease monitoring. Conclusions: Taken together, our screening approach enables broadly applicable cfDNA based precision oncology for patients with advanced cancer through rapid, inexpensive identification of therapeutically relevant CNAs and pre-treatment genomic profiles for disease monitoring, while also guiding additional cfDNA profiling approaches to reserve costly ultra-deep approaches for patients with very low cfDNA tumor content.
Acute promyelocytic leukemia (APL) in pregnancy: A systematic review.
Authors: Samyak Manandhar, Vivek Verma, Smith Giri, Ranjan Pathak, Vijaya Raj Bhatt
Journal: Journal of Clinical Oncology (2015)

e18017 Background: APL is an oncologic emergency requiring prompt treatment. However, the safety of chemotherapy and all-trans retinoic acid (ATRA) in pregnancy is unknown. Methods: A systematic MEDLINE search was conducted to find out all reports with patients with new-onset APL during pregnancy. Additionally, all references of each report were checked. 42 papers with 59 patients were eligible. Results: The majority (76.9%) of patients presented with abnormal bleeding or bruising. All patients were thrombocytopenic, and nearly all anemic and leukopenic. Induction therapy consisted of various regimens of ATRA, cytarabine, and anthracycline. After initial induction therapy, 93.5% of patients achieved complete remission. 52.5% underwent consolidation therapy, mostly cytarabine-based. 6.7% of the patients relapsed, three of whom had not received ATRA. 50% of deliveries were preterm, of which 40.7% were induced. 28.6% resulted in spontaneous or therapeutic abortion. 30.6% of neonates had complications, including respiratory distress syndrome and cardiac arrhythmia. On bivariate analysis, mothers in the first trimester were more likely to experience obstetrical (p = 0.04) but not fetal (p = 0.72) complications. Small number of patients precluded multivariate analysis. At the last follow-up, 94.7% of neonates were developing appropriately. Conclusions: To our knowledge, this is the largest and most recent systematic review of APL in pregnancy. The vast majority of APL patients in pregnancy achieve CR with initial induction therapy. APL in pregnancy, however, is associated with a high risk of fetal complications. Diagnosis of APL during the first trimester diagnosis is predictive of a higher risk of obstetrical complications. These findings indicate that the current therapy is efficacious in pregnant patients with APL but is associated with high risk of obstetrical and fetal complications. The results of our study may help in patient counseling and informed decision-making.
Telomere profile of Reed-Sternberg and Hodgkin cells in diagnostic biopsy in Hodgkin lymphoma as a predictor of clinical response.
Authors: Jeffrey B Tompkins, Cheryl Taylor-Kashton, Celina Li, Matthew Klassen, Haley Stewart, Mary Cheang, Pascal J Lambert, Michel R Nasr, Carmen Morales, Hans Knecht, Donna Ann Wall, Sabine Mai
Journal: Journal of Clinical Oncology (2015)

8541 Background: Markers that predict poor response to primary therapy in Hodgkin’s lymphoma (HL) are currently lacking. Much of the difficulty stems from the rarity of the malignant mononuclear Hodgkin’s (H) cells and multinuclear Reed-Sternberg (RS) cells in the tumor. We have developed a 3D quantitative fluorescent in situ hybridization (3D qFISH) telomere profile, with telomere fluorescent intensity, number, distribution and aggregation, as markers of genomic instability. Telomere profiles differ between H and RS cells; increased genomic instability accompanies the switch from H to RS phenotype. Cases of relapsed/refractory HL have greater H cell genomic instability compared to those entering stable remission. Telomere profiles of H and RS cells at time of diagnosis may predict aggressive disease behavior, as indicated by relapse or refractoriness to therapy. Methods: Incident cases of classical HL from 2002-2010 were retrospectively identified from the provincial cancer registry in Manitoba, Canada. Patients with only palliative treatment or who had insufficient biopsy material for analysis were excluded. Primary outcome was treatment failure (primary refractory, relapse or death from HL). H and RS cell telomeres in the initial diagnostic biopsies were subject to 3D qFISH with telomere specific probes. Resultant images were analyzed with TeloView software. Subhazard ratios (SHR) were computed using competing risk models. Results: 295 patients were diagnosed with HL, of which 145 met the eligibility criteria, and 28 had treatment failure. Median follow up was 4.0 years. H cell mean telomere intensity (SHR 0.77; 95% CI 0.59-1.00; p = 0.048), total telomere intensity (SHR 0.90; 95% CI 0.83-0.98; p = 0.013) and the ratio of RS/H cell total intensity (SHR 1.94; 95% CI 1.43-3.52; p < 0.001), were predictive of treatment failure. RS/H cell total intensity was predictive of outcome while controlling for disease stage (SHR 1.95; 95% CI 1.24-3.05; p = 0.004). Conclusions: Genomic instability of the H and RS cells measured by telomere 3D qFISH is predictive of primary refractory or relapsing HL independent of disease stage and is a potential biomarker of disease behavior at time of diagnosis.
Metabolomic profling in gastric cancer tissues using time-of-flight mass spectrometry.
Authors: Sanae Kaji, Masatoshi Kusuhara, Rie Makuuchi, Yushi Yamakawa, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Kenjiro Kami, Yoshiaki Ohashi, Masanori Terashima
Journal: Journal of Clinical Oncology (2017)

66 Background: To explore carcinogenic and prognostic biomarkers for gastric cancer, genomics, transcriptomics and proteomics approaches have been extensively applied;however, little has been investigated regarding the role of metabolomics profiles on progression and prognosis of gastric cancer. Therefore, in order to elucidate the role of metabolome on prognosis of gastric cancer, we investigated the metabolic profiles of gastric cancer tissue using time-of-flight mass spectrometry (TOFMS) Methods: A total of 162 patients with gastric cancer underwent gastrectomy from February 2010 to March 2013 were enrolled in this study. Cancer tissues (CA) and adjacent non-cancerous tissues (NC) were obtained from surgically resected sample and were snap-frozen in liquid nitrogen. The samples were then homogenized and then applied to capillary electrophoresis TOFMS (CE-TOFMS) The metabolomics dates were analyzed using principal component analysis (PCA) and hierachical clustering analysis(HCA) in order to compare the metabolic profiles of NC and CA. Metabolites date were further assessed according by the non-parametric Mann–Whitney U-test on the presence or absence of recurrence . Results: A total 96 metabolites were detected and quantified. PCA of the date well-distinguished CA from NC. In CA, lactate / pyruvate ratio was significantly higher, while adenylate energy charge was significantly lower than NC, which reaffirms the Warburug effect of cancer. Total glutathione and reducted glutathione/oxidized glutathione ratio in CA were significantly higher than in NC which possibly contributes to the homeostasis of redox status in CA. Intriguingly, in patients with recurrence, tumor concentrations of β-Ala, Asp, GDP and Gly were significantly lower than in those without recurrence. Conclusions: Metabolomic profiling clearly differentiated CA from NC. Considerably high lactate and amino acids levels expectedly highlighted the metabolome of tumors. Certain metabolite will be a candidate for biomarker in gastric cancer.