tbuckley/cabot-search huggingface dataset:
A phase II study on third-line chemotherapy combined bevacizumab with S-1 for metastatic colorectal cancer with mutated KRAS: SAVIOR study.
Authors: Akinori Takagane, Yasuhiro Miyake, Kouji Kobayashi, Naoki Nagata, Atsushi Sato, Yutaka Ogata, Mutsumi Fukunaga, Koki Otsuka, Takao Takahashi, Hidetomo Matsumoto, Yuji Negoro, Yoshihiro Matsubara, Motoki Yoshida
Journal: Journal of Clinical Oncology (2013)

552 Background: Anti-Epidermal growth factor receptor (EGFR) antibody therapy is expected to be effective in treatment for metastatic colorectal cancer (mCRC) with wild-type KRAS, but for mCRC with mutated KRAS, no salvage treatment has been established. We performed a phase II clinical study on 3rd-line chemotherapy combined bevacizumab with S-1, an oral fluorinated pyrimidine preparation containing a dihydropyrimidine dehydrogenase inhibitor, and bevacizumab for mCRC resistant to oxaliplatin and irinotecan. Methods: Subjects were mCRC patients with mutated KRAS, who showed aggravation even after 2 regimens with oxaliplatin and irinotecan. S-1 (80-120 mg/body) was administered for 4 weeks and withdrawn for 2 weeks. The dose of S-1 was decided according to the subjects’ body surface area. Bevacizumab (5 mg/kg) was administered on Days 1, 15, and 29. This treatment was provided until progression. The primary endpoint was disease control rate (DCR), and secondary endpoints were response rate (RR), median progression free survival (mPFS), overall survival (OS), and adverse event (AE). Results: A total of 31 subjects mutated KRAS were enrolled between August 2009 and July 2011. An independent review committee evaluated antitumor effects in eligible 29 of the 31 subjects in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST). Two subjects in whom antitumor effects could not be evaluated were excluded. The DCR was 69% (95% confidence interval [CI], 49.2-84.7%), RR 0% (95% CI, 0-12.3%), mPFS 3.7 months (95% CI, 2.7-6.5 months), OS 9.0 months (95% CI, 7.5-12.0 months), and the median observation period 9.0 months. In 30 subjects for safety evaluation, the incidence of Grade 3 or greater adverse events was 50%. There was no treatment-related death. Major adverse events were anorexia (Grade 3 or greater, 20%), diarrhea (Grade 3, 10%), and decreased hemoglobin (Grade 3 or greater, 16.7%). Conclusions: The results suggest that 3rd-line chemotherapy combined bevacizumab with S-1 is safe and may delay the progression of mCRC resistant to oxaliplatin and irinotecan with mutated KRAS. Clinical trial information: NCT00974389.
Early CMV Infection Detected By Quantitative Nucleic Acid Testing (QNAT) Is Associated with Lower Risk of Relapse after Reduced Intensity, but Not Myeloablative, Hematopoietic Cell Transplantation in Acute Myeloid Leukemia
Authors: Mehrdad Hefazi Torghabeh, Moussab Damlaj, Hassan B Alkhateeb, Raymund Razonable, Aref Al-Kali, Shahrukh K. Hashmi, William J Hogan, Mark R Litzow, Mrinal M Patnaik
Journal: Blood (2015)
Impaired hepatic lipid synthesis from polyunsaturated fatty acids in TM6SF2 E167K variant carriers with NAFLD
Authors: Panu K. Luukkonen, You Zhou, P.A. Nidhina Haridas, Om P. Dwivedi, Tuulia Hyötyläinen, Ashfaq Ali, Anne Juuti, Marja Leivonen, Taru Tukiainen, Linda Ahonen, Emma Scott, Jeremy M. Palmer, Johanna Arola, Marju Orho-Melander, Petter Vikman, Quentin M. Anstee, Vesa M. Olkkonen, Matej Orešič, Leif Groop, Hannele Yki-Järvinen
Journal: Journal of Hepatology (2017)
Safety, immunogenicity, and clinical response of a survivin-based peptide vaccine in therapy-resistant advanced cancer: Results from a phase I/II trial
Authors: J. C. Becker, M. Wobser, V. Hofmeister, B. Bauer, E. B. Broecker, P. thor Straten, M. H. Andersen
Journal: Journal of Clinical Oncology (2008)

3046 Background: Therapeutic vaccination of cancer patients with detectable disease is followed only in few cases by objective tumor regressions despite. This lack of clinical efficacy has been attributed to various immune escape mechanisms including down-regulation or loss of expression of the targeted antigen; hence, antigens essential for the oncogenic phenotype should be more effective. To this end, survivin is essential for the survival of the cancer cell. Methods: The tolerability, immunogenicity, and clinical efficacy of 3 survivin peptides restricted to HLA A1, A2 and B35 were addressed in patients with advanced solid tumors. According to their HLA haplotype patients were vaccinated with 1 to 3 peptides. 3 consecutive vaccination protocols were tested: (i) 100 μg of peptide emulsified in Montanide ISA-51 as deep s.c. injections on d1, d8, d28, and then every 28 days, (ii) weekly injections until d56 followed by monthly injections, and (iii) the latter schedule preceded by a single i.v. bolus of 250 mg/m2 cyclophosphamide. Results: In total, 79 patients with metastatic melanoma (n=61), pancreatic (n=8), cervical (n=5), colorectal (n=2), adrenal gland (n=2), and merkel cell carcinoma (n=1) who failed to respond to systemic standard therapy were included. Frequently observed toxicities included transient grade 1/2 injection site reactions, grade 1 fever and painless swelling of the lymph nodes draining the vaccination site. No signs of autoimmunity or impaired wound healing were observed. Vaccine-specific immune responses were induced in 50% of the patients with a trend to a higher responder rate in the frequency-intensified schedules, which was not further increased by addition of prior cyclophosphamide. Clinical virtue, i.e. objective responses and control of disease, were essentially restricted to immunological responders. 3 complete responses and 3 partial responses were observed with duration of response ranging from 3 to 36+ months (OR=7.6%). Conclusions: Peptide vaccination against the inhibitor of apoptosis protein survivin is safe and elicits tumor specific CD8+ T cells. Encouraging clinical responses in these patients with therapy-refractory cancer warrants further development of this vaccine. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck Merck
Primary non-Hodgkin’s lymphoma of the breast: First report of the multicentre retrospective study of the International Extranodal Lymphoma Study Group (IELSG-15)
Authors: G. F. Ryan, G. Martinelli, K. Yuen, J. Seymour
Journal: Journal of Clinical Oncology (2005)

6575 Background: Primary breast lymphoma is a rare poorly-defined condition. This large multi-centre retrospective review investigates its prognosis and patterns of relapse. Methods: Patients presenting with histologically-proven primary non-Hodgkin’s lymphoma of one or both breasts between 1980 and 2003 are included. Data was obtained retrospectively from patient medical records. Central histology review was undertaken where possible. Survival curves were estimated using the Kaplan-Meier method, and prognostic factors analysed by univariate and multivariate analysis. The major study endpoints were progression-free and overall survival. Results: A total of 276 eligible patients were identified. Of these, 202 patients had diffuse large B-cell histology, and form the basis of this analysis. Sixty-seven percent of patients had Stage IE disease, 28% were stage IIE, and 5% were stage IVE(bilateral). B-symptoms were present in 4%. International Prognostic Index (IPI) was 0,1,2 and 3 in 27,37,15 and 3%, respectively. Eighty percent of patients received chemotherapy, 64% radiotherapy, and 50% both, with 87% of patients achieving a complete response at the end of planned first-line therapy. Thirty-seven percent of patients subsequently progressed in one or more sites. The crude rates for recurrence in breast, loco-regional nodes, and central nervous system (CNS) were 15%, 6%, and 5%. Only one breast relapse occurred in an irradiated breast. The median progression-free survival was 5.9 years (95% CI: 3.7, 8.0), with a median follow-up duration of 5.5 years. Median overall survival was 8.4 years (95% CI: 6.5, 10.9). The only statistically significant prognostic factor on multifactor analysis was IPI. Conclusions: The outcome for patients presenting with primary diffuse large B-cell non-Hodgkin’s lymphoma of the breast was significantly worse than that anticipated for Stage I and II nodal lymphomas treated during a similar period. The data suggests that future prospective studies should investigate intensification of treatment, and that the addition of specific prophylactic therapy targeted at the major sites of recurrence may improve prognosis. No significant financial relationships to disclose.
Combination Immunotherapy with a CpG Oligonucleotide and Rituximab (R) Augments the Immunological Response and Favorably Alters the Malignant Microenvironment of Follicular Lymphoma (FL).
Authors: Jonathan W. Friedberg, Jennifer Kelly, Jeffrey L. Kutok, Rabih Salloum, David C. Fisher, Elizabeth Ronan, Virginia Dalton, Lynn Rich, Diana Marquis, Paul G. Rothberg, Jane Liesveld, Richard I. Fisher, Robert Coffman, Tim Mosmann, Arnold S. Freedman
Journal: Blood (2006)
A controlled, multicenter randomised phase 3 study of an extended release miconazole (50mg) bioadhesive buccal tablet once daily for local treatment of oropharyngeal candidiasis in head and neck cancer patients undergoing radiation therapy
Authors: R.-J. Bensadoun, D. Daoud, L. Bastit, B. El Gueddari, C. Allavena, A. Benidder, R. Gourmet, S. Ghabri, C. Chaumont, J.-F. Dufour-Lamartinie
Journal: Journal of Clinical Oncology (2005)

5527 Background: Oropharyngeal candidiasis (OPC) is the most frequently occurring infection in head and neck cancer (HNC) patients undergoing radiation therapy (RT). Methods: Patients (pts) who had completed RT for HNC at least 6 weeks before entering the study, with OPC confirmed by direct exam or fungal culture were included in 27 French and 9 North African centers. Pts with disseminated candidiasis, having received systemic antifungal agents within less than 14 days were excluded. Group A received the bioadhesive buccal tablet containing 50mg of miconazole (MBBT) qd and group B a buccal gel (MBG) containing 125mg of miconazole q.i.d. for 14 days. A sample size of 103 pts per arm was required to obtain a 90% power to demonstrate non-inferiority of MBBT compared with MBG (α level of 5%, δ of 20%, 2 one sided). Primary endpoint was success at D14, defined as complete (CR) or partial (PR) clinical response. Response was based on the score of oral lesion (0 = none, 1 = single localised, 2 = multiple localised, 3 = extensive or confluent). Response was assessed by the investigator and a blind evaluator. Results: The 282 pts (A=141, B=141) in the modified intent-to-treat (MITT) group included all pts receiving at least one day of treatment and with one efficacy data point. The per-protocol (PP) population was composed of 213 pts with a validated, blinded evaluation of the primary endpoint (A=106, B=107). Null hypothesis that MBBT is inferior to MBG is rejected at the 2.5% level of significance. Conclusions:The efficacy of the Bioadhesive Buccal Tablet (miconazole Lauriad) is achieved with 10 times less (50 mg vs 500 mg) miconazole and on a more convenient schedule (once vs four times per day) than the gel, suggesting the potential for better patient compliance in treating OPC in pts with altered mucosa and xerostomia. Group A miconazole bioadhesive tablet 50 mg qd Group B miconazole gel 125mg q.i.d p value Non-inferiority margin (97.5%) 95% CI MITT CR+PR 70/141 (49.7%) 70/141 (49.7%) 0.0004 11.9% [-11,9%; 11,9%] (282 pts) CR 64/141 (45.4%) 64/141 (45.4%) 0.0004 11.8% [-11.8%; 11.8%] PP (blind evaluation) CR+PR 54/107 (50.5%) 58/106 (54.7%) 0.0112 17.9% [-9,4%; 17.9%] (213 pts) CR 48/107 (44.9%) 53/106 (50%) 0.0152 18.6% [-8.6%; 18.6%] Sensitivity analysis CR+PR 69/137 (50.4%) 69/135 (51.1%) 0.0008 12.8% [-11.3%; 12.8%] (272 pts) CR 63/137 (46%) 63/135 (46.7%) 0.0007 12.6% [-11.4%; 12.6%] Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bio Alliance Bio Alliance
Neoadjuvant ixabepilone/carboplatin/trastuzumab in HER2-positive locally advanced breast cancer: A Sarah Cannon Research Institute phase II trial.
Authors: J. D. Zubkus, D. B. Daniel, J. F. Eakle, R. G. Bechhold, M. Shastry, P. S. Tucker, H. A. Burris, J. D. Hainsworth, D. A. Yardley
Journal: Journal of Clinical Oncology (2011)

621 Background: The combination of docetaxel, carboplatin, and trastuzumab (TCH) is a standard adjuvant and neoadjuvant regimen for patients (pts) with HER2-positive breast cancer. Ixabepilone is a microtubule stabilizer active in taxane-refractory metastatic breast cancer (MBC) and in the neoadjuvant setting, where ixabepilone monotherapy yielded a pathologic complete response rate (pCR) of 18%. In HER2 + MBC, weekly ixabepilone with carboplatin plus trastuzumab yielded a 44% response rate. We evaluated ixabepilone in lieu of docetaxel in the TCH regimen as neoadjuvant treatment in HER2+ breast cancer. Methods: Eligibility criteria: locally advanced (clinical T1-T3, N0-N2, M0) breast adenocarcinoma, HER2+ (IHC3+ or FISH > 2), ECOG PS ≤2, and normal LVEF. Pts received ixabepilone 40 mg/m2, carboplatin AUC=6, and trastuzumab 6mg/kg (8mg/kg loading dose) IV on day 1 q21 days x 6 cycles. Tumor assessments were performed after 3&6 cycles. Definitive surgery and trastuzumab to complete a 12-month course followed. Radiation and/or antiestrogen therapy was prescribed per institutional guidelines. pCR (no residual invasive cancer in breast or lymph nodes) was the primary endpoint. Results: 41 women (median tumor size 2.8 cm, ER-/PR- 54%) were treated from 4/09 – 4/10. 83% completed 6 cycles of neoadjuvant treatment. 7 pts did not complete 6 cycles, 5 due to toxicity (hematologic – 2 pts; nonhematologic – 3 pts) and 1 due to disease progression. One pt with a clinical CR went to surgery after 4 cycles. 36 pts had definitive surgery (mastectomy 64%, breast conservation 36%), 21 pts (58%) achieved pCR; 2 pts had CR at the primary site (with residual involved nodes). 1 pt progressed post surgery while receiving adjuvant trastuzumab. Grade 3/4 toxicities were primarily hematologic, including: neutropenia (80%), anemia (34%), thrombocytopenia (27%), neuropathy (12%), nausea/vomiting (17%), diarrhea (10%), and febrile neutropenia (5%). No cardiotoxicity occurred. Conclusions: The combination of ixabepilone, carboplatin, and trastuzumab as neoadjuvant therapy was well-tolerated with similar pCR rates to other neoadjuvant taxane/trastuzumab-containing combinations.
Demonstration of subpopulations with differing cancer stem cell phenotypes in xenograft and in vitro models of colorectal liver metastases.
Authors: Dominic E. Sanford, Andrew Giorgi, Brian D. Goetz, Roheena Z. Panni, William G. Hawkins, David Linehan, Peter S Goedegebuure, Ryan C. Fields
Journal: Journal of Clinical Oncology (2013)

394 Background: Tumors are composed of heterogeneous cell populations, some of which demonstrate enhanced tumor-forming capabilities (so-called tumor initiating cells [TIC] or cancer stem cells). In colorectal cancer (CRC), CD133, 44, and 24 are cell surface markers that identify TIC. Therefore, we sought to determine if CRC liver metastases (CRC-LM) form xenografts (in vivo) and cell cultures (in vitro) with TIC markers. Methods: CRC-LM were grafted in NOD/SCID mice and passaged serially. Xenografts were mechanically dissociated and cultured under sphere forming conditions. Flow cytometry was performed for TIC phenotype. Results: 16 of 18 (89%) CRC-LM specimens formed tumors in mice. Xenografts formed EpCAM+ tumors and spheres. The frequency of CD133+, CD44+, and CD133+/CD44+ tumor cells were 55%, 33%, and 23%, respectively. There was a subpopulation of CD133+/CD44+ cells with elevated CD44 expression(CD44hi). This CD133+/CD44hi population was also CD24+; representing 5% of cells. Eight of eleven (73%) xenografts formed spheres in vitro. The frequency of CD133+, CD44+, and CD133+/CD44+ cells were 63%, 47%, and 26%, respectively. CD133+/CD44+/CD24+ cells made up 8% of sphere-forming cells. There was a non-significant trend towards increased frequency of CD133+, CD44+, and CD133/CD44 positive cells in the spheres compared to the xenografts. However, the percentage of CD133+/CD44+/CD24+ cells was significantly increased in spheres relative to xenografts (8% vs. 5%, respectively; p&lt;0.05) (see Table). Conclusions: CRC-LM derived xenografts and spheres are composed of distinct cell populations with differing levels of TIC/cancer stem cells. Sphere cultures may enhance for the most enriched TIC population. Thus, xenografts and sphere cultures are important model systems to further study the importance of cancer stem cells in CRC progression and metastases. [Table: see text]
Predictive factors for symptomatic radiation pneumonitis in 293 consecutively treated non-small cell lung cancer (NSCLC) patients receiving definitive radiation therapy.
Authors: A. Orisamolu, E. Xanthopoulos, A. Fernandes, J. P. Christodouleas, S. Apisarnthanarax, N. Mitra, F. Wan, C. J. Langer, T. L. Evans, J. Stevenson, D. Sterman, A. Vachani, A. R. Haas, R. Rengan
Journal: Journal of Clinical Oncology (2011)

7041 Background: Radiation pneumonitis is a potentially fatal complication in NSCLC patients treated with definitive radiotherapy. The ability to identify patients at risk for this complication would be of value to clinicians. The objective of this study was to identify significant predictors of grade 2 or higher radiation pneumonitis. Methods: Consecutive NSCLC patients receiving definitive non-stereotactic radiotherapy at the University of Pennsylvania between January 2003 to July 2010 were graded for post-treatment radiation pneumonitis using RTOG criteria. Demographic and treatment data were collected on all patients. Univariate and mutivariate analysis was used to determine predictors of grade 2 or higher pneumonitis. Results: Of 293 patients treated in this period, 47% were male, 52% received concurrent chemotherapy. Median prescription dose was 66.6Gy, median gross tumor volume was 91cc, and the median mean lung dose (MLD) was 16Gy. On univariate analysis, concurrent chemoradiation (p = 0.002; OR 2.7), MLD (p = 0.0001, OR = 1.14/Gy), KPS (p = 0.045, OR = 1.04/point), and N2/3 disease (p = 0.026, OR = 2.51) were significant predictors of pneumonitis. A multivariate analysis including all significant predictors on univariate analysis was performed and only MLD (p = 0.031, OR = 1.10/Gy) proved significant. The median MLD cutoff of 16Gy had a sensitivity/specificity of 72% and 55% respectively and positive and negative predictive value of 55% and 87% respectively. Of note, V20 (volume of lung receiving 20Gy or higher), smoking status, and pre-treatment pulmonary function tests including FEV1 and DLCO were not significant predictors of pneumonitis. Conclusions: MLD was a significant predictor of grade 2 or higher radiation pneumonitis in patients with NSCLC receiving definitive radiotherapy, while V20 was not. Additionally, the poor positive predictive value and specificity of MLD limits the clinical utility of this variable. This study underscores the need for more robust predictors of radiation pneumonitis.
Patients’ perception of long-term, low-molecular weight heparins for cancer-associated thrombosis (CAT): Treatment expectations, convenience, and satisfaction related to patient profile.
Authors: Francis Cajfinger, Dominique Farge-Bancel, Nicolas Falvo, Marie-Antoinette Sevestre, Anne Lamblin
Journal: Journal of Clinical Oncology (2015)

88 Background: In the TROPIQUE study CAT pts had high expectations for anticoagulant treatment &amp; long-term LMWH was perceived as convenient with high degree of treatment satisfaction. In this study, using the Perception of Anti-Coagulant Treatment Questionnaires (PACT-Q), we assessed the inpact of patient profile on treatment expectations, convenience and satisfaction. Methods: PACT-Q (1&amp;2) were proposed on a voluntarily basis to cancer pts recently diagnosed with symptomatic venous thromboembolism; the global mean scores±SD was correlated to pts characteristics. Results: 269 PACT-Q1 &amp; 139 PACT-Q2 were analysed &amp;135 pts done both of them. In all pts, the highest mean scores were for expectations of symptom relief (4.22±0.9), confidence in preventing clots (3.98±1.04) &amp; importance of simplicity of use (3.94±0.75). For clot prevention men were more confident (4.06±0.81) vs women (3.85±0.88). Expectations of symptom relief was higher in women (4.07±0.98) vs men (3.89±1.09). Importance of ease of use was higher in treated pts (4.27±0.89) vs no therapy (4.00±0.99) &amp; pts with age ≥ 49 (4.46±0.59) vs &lt; 49 years (3.98±1.07). At the end of the study, PACT-Q2 answers showed, an Anticoagulant Treatment Satisfaction scores of 62.9±16.7. 67.2% of pts felt strongly reassured &amp; 48.5% were satisfied with symptom decrease. 69.1% of pts were satisfied / very satisfied with their anticoagulant treatment. Treatment-related side effects were as expected (41.7%), better/much better than expected (45.5%). 80.6% of pts reported higher ease with tinzaparin and 76.2% with other LMWH. According to pts characteristics, satisfaction was higher in men (64.4±17.7) vs women (61.0±15.0), in non-metastatic (64.6±16.9) vs metastatic (61.1±16.2). ECOG (3-4) pts reported lower treatment convenience with higher satisfaction vs ECOG (0-1); 80.0% of ECOG (3-4) pts were satisfied/very satisfied with anticoagulant treatment. 70.0% of ECOG (1-0) patients stated symptom decrease &amp; 80.0 % a feeling of reassurance. Conclusions: pt’s profile influenced positively the perception of long-term LMWH treatment but not the convenience &amp; treatment satisfaction.