tbuckley/cabot-search huggingface dataset:
Derivation of a second generation multivariate index assay to improve specificity in pre-surgical evaluation of adnexal masses for risk of ovarian malignancy.
Authors: Zhen Zhang, Todd Pappas, Lori J. Sokoll, Alan Smith, Li Chen, Daniel W Chan, Donald Gordon Munroe
Journal: Journal of Clinical Oncology (2015)

5561 Background: The FDA cleared in vitro diagnostic multivariate index assay OVA1, with its intended utility to assist in referral of high risk patients to gynecologic oncologists, was by design to have a high sensitivity in assessing risk of malignancy in patients diagnosed with an adnexal mass prior to planned surgery. In this study, we developed and evaluated a second generation multivariate index assay (MIAG2) to improve specificity while maintaining a level of sensitivity similar to OVA1. Methods: CA 125 II, prealbumin, apolipoprotein A-1 (ApoA1), beta 2-microglobulin, transferrin (TRF), follicle-stimulating hormone (FSH), and Human epididymis protein 4 (HE4) were retrospectively analyzed on serum samples from a prospective multicenter study of patients with a documented pelvic mass planned for surgery. The samples were divided by block randomization into a training set (pre-/post-menopausal: 130/150; benign: 174, malignant: 106 including 35 stage I/II and 16 low malignant potential (LMP) cases) and a preliminary validation set (pre-/post-menopausal: 154/151; benign: 233, malignant: 72 including 19 stage I/II and 13 LMP cases). Results: Selected through extensive statistical resampling, the MIAG2 panel consists of CA 125 II, ApoA1, TRF, FSH, and HE4. Its algorithm uses two ensembles of classification models, for pre- and post-menopausal women respectively. However, with the help of FSH, the outputs of the models were integrated into a single-valued index with a cutoff of 5.0 arbitrary units for all patients. The specificity and sensitivity of the MIAG2 for the validation set were 60.1% (140/233) and 88.9% (64/72), respectively, compared to OVA1 which had a specificity of 47.2% (110/233) at a sensitivity of 95.8% (69/72). The improvement in specificity was statistically significant (p < 0.001). It is of interest to note that both the MIAG2 and OVA1 had a high sensitivity in detecting non-LMP ovarian cancer at 96.6% (57/59) and 100.0% (59/59), respectively. Conclusions: The MIAG2 significantly improved specificity over that of OVA1 while maintaining a comparably high sensitivity in pre-surgical assessment of adnexal masses for risk of malignancy.
Racial differences in <i>KRAS</i>/<i>BRAF</i> mutation rates and survival in colon cancer (NCCTG N0147 [Alliance]).
Authors: Harry H. Yoon, Qian Shi, Steven R. Alberts, Richard M. Goldberg, Stephen N. Thibodeau, Daniel J. Sargent, Frank A. Sinicrope
Journal: Journal of Clinical Oncology (2014)

3536 Background: It is unknown if racial disparities in colon cancer outcomes persist after controlling for clinicopathologic variables and treatment. Molecular characterization of colon cancers in a North American population that includes Asians has not been reported. Methods: KRAS/BRAF mutation (mt) was determined in stage III colon cancer patients (pts, N = 3305) in the North American phase 3 adjuvant trial N0147. Race categories included Asian (149), black (240), or white (2916). Outcomes were analyzed in 2931 pts randomized to FOLFOX +/- cetuximab. Given a lack of interaction between race and treatment, arms were pooled. Cox models were used to estimate disease-free survival (DFS). Results: BRAF mt frequency in tumors from whites was twice that of tumors from Asians or blacks; KRAS mt rates were highest in tumors from blacks; KRAS/BRAF wildtype (wt) rates were highest in tumors from Asians (all P <.005; Table). Compared to whites, tumors from blacks were more likely to be N1 (vs N2) or low-grade (vs high), and tumors from Asians were more likely to be distal (vs proximal) (all P <.003). Blacks were younger than whites (P <.001). Notably, the prognostic impact of race differed based on N stage (Pinteraction =.0049) and age (Pinteraction =.012). Thus, DFS was analyzed by N stage (Table) and age. Blacks had shorter DFS than whites among N1 pts, and Asians had longer DFS among N2 pts, independent of covariates including KRAS/BRAF (Table). Among age <50, blacks had shorter DFS than whites (multivariate HR 2.8; 95% CI 1.7-4.6; P<.0001). Findings were consistent using time to recurrence as the outcome. Conclusions: These data, to our knowledge, are the first to show that Asians have a significantly lower rate of KRAS/BRAF mutations than blacks or whites. We also report a novel interaction of race with N stage and age, showing that racial disparities in survival persist despite uniform stage and enrollment in a phase 3 trial. Race Mt rates DFSa N1 subset N2 subset BRAF mt KRAS mt WT for both Poverall HR 95% CI P HR 95% CI P Asian 6% 28% 67% <.0001 .94 .43, 2.02 .87 .50 .25, .99 .045 Black 6% 44% 50% 1.54 1.04, 2.29 .032 .96 .60, 1.52 .85 White 14% 35% 51% ref ref a Adjusted for KRAS/BRAF, mismatch repair, T stage, grade, tumor site, age, body mass index, smoking.
포스터전시 : 70세 이상 고령 환자에서 간세포암의 임상 양상 (초)
Authors: 이경인, 권영란, 김윤정, 서혜진, 김은수, 장병국, 정우진, 박경식, 조광범, 황재석
Journal: Clinical and Molecular Hepatology (2010)
Natural history of multiple myeloma (MM) relapsing after autologous stem cell transplantation (ASCT)
Authors: S. Madan, S. Kumar, M. Q. Lacy, A. Dispenzieri, S. R. Hayman, F. K. Buadi, D. Dingli, S. V. Rajkumar, M. A. Gertz
Journal: Journal of Clinical Oncology (2009)

e19513 Background: The outcome of patients with MM relapsing after ASCT used early in the disease course or after failure of initial therapy, is not well defined. We undertook this study to understand treatment approaches for patients relapsing after single ASCT. Methods: Patients relapsing after single ASCT were identified from a prospectively maintained database and relevant clinical data were extracted from medical records. Relapse and treatment responses were according to IMWG Uniform Response Criteria. Patients relapsing between Jan 2000 and 2008 were included in order to capture a recent cohort contemporaneous to availability of novel drugs. Results: We studied 487 patients who had relapsed following a single ASCT, of whom 351 (72%) had an early SCT (≤ 12 mos from diagnosis). The median estimated follow up for all patients was 27 mos, 50 mos and 69 mos from relapse, SCT and diagnosis respectively. The median overall survival (OS) from the time of relapse was 30 mos for the early SCT group and 21 months for the late SCT group. The median time to relapse following transplant was 15 mos (3–119) among early SCT group and 12 mos (3–76) among the late SCT group. Longer time to relapse as well as longer time from relapse to initiation of therapy were independent predictors of better outcome. Among the early group, nearly a third of the patients achieved a PR or better to first salvage therapy (Table), with another third achieving stable disease and 25% of patients did not have response data. The median progression free survival for the first salvage regimen was 8 mos; 18 mos for those with PR or better and 5 mos for those with SD as the best response. Data on the regimen 2, 3, 4, 5, and 6 were available for 211, 133, 84, 53 and 28 patients respectively. As expected, the response rates and the response duration decreased with increasing number of relapses. Conclusions: Patients relapsing after ASCT can obtain prolonged response duration with the currently available treatments. Those with a durable response to transplant and those not requiring initiation of therapy for long periods after disease relapse have favorable disease biology and have prolonged survival after relapse. The natural history of the disease provides a valuable benchmark for evaluation of newer treatment approaches. No significant financial relationships to disclose.
Clinical pharmacokinetics of simotinib, an oral EGFR tyrosine kinase inhibitor,in patients with advanced NSCLC patients.
Authors: Xiaohong Han, Ning Li, Xingsheng Hu, Yuanyuan Song, Yan Zhang, Yuankai Shi
Journal: Journal of Clinical Oncology (2015)

e13575 Background: Simotinib is an innovative small molecule EGFR TKI (WO 2007/084875), which was chemically synthesized by Advenchen Laboratories LLC (Northridge, USA).To date, erlotinib and gefitinibwere the only two small-molecule EGFR TKIs approved for the therapy of NSCLC by FDA. Icotinib hydrochloride (ZhejiangBeta Pharma Inc., Hangzhou, China), is a potent and reversible EGFR TKI that gained approval for treatment of NSCLC in China in 2011.The purpose of the present study was to investigate the pharmacokinetics of simotinibin in patients with NSCLC for the first time (NCT01772732). Methods: Oral simotinib was supplied by JiangsuSimcerePharmaceutical R&D Co. Ltd (Jiangsu, China)as tablets containing 50 mg and 150 mg.Dose escalation of simotinib followed a standard 3 + 3 design.Different doses (100-500 mg) of oral simotinib were administered twice daily (Q12H) for a 28-continuous-day cycle, and 15 patients participated in the study at present. Blood samples for pharmacokinetic measurements were taken on day 1 after the first dose (equivalent to a single-dose evaluation) and on day 15 for multiple-dosing evaluation; measurement times included the following: pre-dose and at 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12h on days 1 and 15. On days 8, 9 and 10, predose samples were collected to check the trough level. Results: Plasma concentration of simotinib reached peak at a median Tmax of 1.0–6.0 h after single dose and then declined with a mean T1/2 of 4.7–11.1 h, which was consistent over the five dose levels. Over the dose range of 100–500 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases.The concentrations of simotinib on days 8,9, and 10 predose samples were consistent with Claston day 15 indicating a probable steady state.The individual accumulation ratio based on theAUCranged from 1.3 to 2.5, suggesting that simotinibaccumulates in the body to a certain extent after daily administrationfor15 days. Conclusions: Simotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range.T1/2 of simotinib was consistent with icotinib, but simotinib showed a more stable Cmin than icotinib. Clinical trial information: NCT01772732.
Relevance of a medicosurgical strategy combining cetuximab and chronomodulated (Chrono) chemotherapy (chemo) with metastases resection as 3rd line treatment for patients (pts) with metastatic colorectal cancer (MCRC)
Authors: A. Karaboue, M. Bouchahda, R. Adam, P. Innominato, M. P. Bralet, T. Moreau, D. Hauteville, C. Guettier, F. Levi
Journal: Journal of Clinical Oncology (2007)

14505 Background: Metastases surgery offers long tem survival for pts with chemo-downstaged MCRC (Adam et al. Ann Surg 2004). The relevance of this medicosurgical strategy was investigated in pts given cetuximab (Cetux) and Chrono after chemo failure. Methods: 56 pts with progressive MCRC on prior chemo received Cetux (400 mg/m 2 on 1 st dose then 250 mg/m 2 /week) and q2w Chrono based on irinotecan (34 pts), oxaliplatin (14 pts) or both (8 pts). Toxicity grades (G) and response were assessed q2w and q8w, respectively. Tumour EGFR was determined by immunohistochemistry (all pts) and gene copies by fluorescence in situ hybridisation (27 pts). Metastases surgery was attempted whenever complete resection was foreseen. Results: Median of 3 prior chemo (1 to 8); median age: 61 years (35 to 79); M/F: 34/22; WHO PS 0/1/2/3: 37/14/4/1; colon/rectum: 32/24; M sites 1/2/=3: 15/22/19; liver/lung: 45/40. EGFR was detected in the tumor of 39 pts (69.6%). 3 pts had G4 allergy. 53 evaluable pts received a median of 5 courses of Cetux-Chrono (1–22). G2–3 acneiform rash occurred in 36 pts (67.8%; G3: 30.4%). Main G3–4 toxicities were diarrhea (26.5%), neutropenia (23.1%) and neuropathy (22.6%). The objective response rate (ORR) was 32% [95% CI, 19.4 to 44.6] (13 PR and 3 CR). ORR was correlated positively with acneiform rash (p= 0.019) but negatively with the detection of EGFR+ tumor cells (0%, ORR=54.5%; 1–10%, 33%; &gt;10%, 16.7%; p = 0.044). No EGFR amplification was documented including 8 OR. Median progression-free survival (PFS) and overall survival were 5.1 [3.2–6.9] and 13.9 months [6.5–21.3] respectively. Metastases surgery was performed in 10 pts (8 R0, 2 R1) after 3–15 courses of Cetux-Chrono as 2 nd -5 th line. Median PFS in resected pts was 11.7 months [5.8–17.6], with a survival estimate of 80% at 21 months. Conclusions: Cetux-Chrono safely reverted MCRC resistance and allowed successful metastases resection in 17.8% of these pts, like 1 st line chemo. This medicosurgical strategy impacted favourably on long term survival, despite its application as 3 rd treatment line. Supported by ARTBC, Hôpital Paul Brousse, Villejuif, France No significant financial relationships to disclose.
Evidence-based adjuvant chemotherapy for NSCLC in southeastern United States.
Authors: Dinah Faith Q Huff, Marc L. Fishman, Sharon Davis, William S. Shimp, Charles L. Bennett, Jurgen Kogler, Anna E. Schorer, Laura Rose Bobolts, Melissa Armitage, William J. Hrushesky
Journal: Journal of Clinical Oncology (2014)

e18504 Background: Adjuvant chemotherapy is recommended for certain non-small cell lung cancer (NSCLC) patients in effort to improve survival and prevent disease recurrence. Many patients can be cured by resection alone, while others may succumb to the disease despite adjuvant therapy. Risk-benefit considerations demand that improved survival be the gold standard for administering adjuvant chemotherapy for NCSLC patients. Methods: We systematically searched PubMed for randomized controlled trials on adjuvant chemotherapy for NSCLC published between 1995 and 2012. We also reviewed all adjuvant NSCLC chemotherapy requests from 2,800 oncology practices from a major health insurer in the Southeast, from April 2009 through December 2013. We limited this analysis to adjuvant therapy in stage I or stage II NSCLC patients. Results: All level 1 data show and five national guidelines recommend that stage II patients are most likely to benefit from adjuvant chemotherapy, while stage I patients are more likely to be harmed. In our sample 24% (54 of 227) of adjuvant chemotherapy requests were made on behalf of stage I NSCLC patients. All randomized controlled trials demonstrate only cisplatin- and not carboplatin-based regimens confer survival advantage. Despite this evidence, 73% (165 out of 227) adjuvant therapy requests were made for carboplatin-based regimens with no change in platinum agent usage over four years. Conclusions: Many NCSLC patients in the southeast are treated for stages, or with regimens, unsupported by survival evidence. Oncology Analytics, our utilization management organization, is instituting quality improvement initiatives to address this apparent regional need and will compare findings between stage IA and IB disease.
An oral methionine aminopeptidase II inhibitor for high-risk non-muscle invasive bladder cancer relapsed after intravesical therapies: Update of a phase II trial.
Authors: Dingwei Ye, Xudong Yao, Gongxian Wang, Jinxian Pu, Xin Yao, Fangjian Zhou, Jun Qi, Zhangqun Ye, Liping Xie, Jimin Chen, Keji Xie, Xiaokun Zhao, Zhihui Xu, Hongqian Guo, Yong Yang, Dalong Cao, Bin Yang, Cheng Zhang, Yong Lu, Jun Du
Journal: Journal of Clinical Oncology (2017)

303 Background: In 2016, we reported the preliminary results of APL-1202, an oral MetAP2 inhibitor, in the first 18 patients enrolled in the phase II trial. The purpose of the present study is to update the results of efficacy, safety, pharmacokinetics at steady state and translational studies in 41 patients. Methods: This is an open-label, single-arm phase II trial conducted in 15 hospitals in China. High-risk in recurrence is defined according to EORTC recurrence score and probability tables in EAU 2012 Guidelines on NMIBC. The primary end point is the recurrence-free survival rate at 1 year. Plasma and urine samples at steady state were collected for pharmacokinetic studies, and separate plasma samples were collected for translational studies. Results: From May 2014, a total of 41 patients have been enrolled in this study, including 39 relapsed after intravesical chemotherapies only (chemo-failed subgroup), and 2 after both chemo and BCG treatments (BCG-failed subgroup). All of patients had TaT1 papillary tumors, and 3 with concurrent carcinoma in situ . APL-1202 did not cause any drug-related SAEs. By the time of this abstract submission, the 1-year recurrence-free rate is 54.3% (37.2-73.2%, 95% Confidence Interval) with a median recurrence-free survival of 14.7 months. APL-1202’s plasma exposure at steady state appears to increase proportionally to the increase of doses. Conclusions: APL-1202 is safe and well tolerated at a daily dose up to 750mg, TID, for 12 weeks followed by 3 months on-and-off in patients with recurred high-risk NMIBC. According to the EAU 2012 Guidelines on NMIBC, naïve high-risk NMIBC patients treated by intravesical chemotherapies have a 1-year recurrence-free rate of 39% (33-45%, 95% CI) with a median recurrence-free survival of 9 months. Our results support the concept that oral MetAP2 inhibitor APL-1202 as a second-line therapy has the potential to achieve at least similar efficacy with the first-line intravesical chemotherapies, and warrant a randomized trial alone or in combination with other therapies in NMIBC patients. Clinical trial information: CTR20131716.
Unexpected viral relapses in hepatitis C virus–infected patients diagnosed with hepatocellular carcinoma during treatment with direct‐acting antivirals
Authors: Alessandro Soria, Massimiliano Fabbiani, Giuseppe Lapadula, Andrea Gori
Journal: Hepatology (2017)

Soria, Alessandro; Fabbiani, Massimiliano; Lapadula, Giuseppe; Gori, Andrea Author Information
Phase II study of erlotinib plus tivantinib in patients with <i>EGFR</i>-mutation–positive NSCLC who failed in immediately previous EGFR-TKI therapy.
Authors: Tomonori Hirashima, Koichi Azuma, Nobuyuki Yamamoto, Toshiaki Takahashi, Makoto Nishio, Taizo Hirata, Kaoru Kubota, Kazuo Kasahara, Toyoaki Hida, Hiroshige Yoshioka, Kohei Suzuki, Shiro Akinaga, Kazuto Nishio, Tetsuya Mitsudomi, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2014)

8052 Background: Although driver mutations in EGFR gene are often associated with initial dramatic response to EGFR-TKI, those patients inevitably develop acquired resistance. It is suggested that dual inhibition of EGFR and c-Met may overcome or delay emergence of this resistance. Therefore, we conducted a multicenter, open-label, single arm Phase II combining erlotinib and a c-Met inhibitor tivantinib, in EGFR-mutated NSCLC patients with EGFR-TKI resistance. Methods: NSCLC patients who developed progressive disease during their immediately previous treatment with either erlotinib or gefitinib were enrolled. Fresh tumor biopsy was mandatory prior to starting the combination. All patients received daily oral erlotinib and tivantinib, until discontinuation criteria were met. Tumor response was evaluated by the independent radiological committee. The biopsy specimens were used for a comprehensive biomarker analysis, such as IHC assay of c-Met and HGF, and for multiplex mutation analysis (LungCarta Panel) of lung cancer associate genes including KRAS, c-MET, PTEN, EGFR and TP53. Plasma concentration of soluble c-Met and 8 angiogenic cytokines were also determined by ELISA and Luminex assay, respectively. Results: Forty-five patients were treated. The Table below shows objective response rate (ORR) and progression free survival (PFS) in the overall population, and in a subpopulation defined by c-Met expression or resistance mutations in EGFR (i.e. T790M or Exon 20 ins). Most of AEs were similar to the previous trials. Conclusions: In patients with EGFR-mutated NSCLC with EGFR-TKI resistance, erlotinib/tivantinib combination therapy may be beneficial to those with high c-Met expression or in those without resistance mutations in EGFR. The more detailed multivariate analyses regarding biomarkers will also be reported. Clinical trial information: NCT01580735. Population N ORR (%) Median PFS (days) Overall 45 4.4 (95% confidence interval [CI]; 0.5-15.1) 83 (CI; 43-128) c-Met high 22 9.1 (CI; 1.1-29.2) 125 (CI; 43-212) c-Met low 22 0.0 (CI; 0.0-15.4) 43 (CI; 42-127) Resistance mutations positive 23 0.0 (CI; 0.0-14.8) 44 (CI; 42-129) Resistance mutations negative 22 9.1 (CI; 1.1-29.2) 86 (CI; 43-132)
Intensity modulated radiotherapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) for children with head-and-neck rhabdomyosarcoma
Authors: S. E. Combs, W. Behnisch, A. Kulozik, M. W. Muenter, J. Debus, D. Schulz-Ertner
Journal: Journal of Clinical Oncology (2006)

9065 Background: To evaluate intensity-modulated radiotherapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) for children with head-and-neck rhabdomyosarcoma (RMS) with special regard to radiation induced toxicity. Methods: From 1995 to 2005, we treated 19 children with head-and-neck RMS with FSRT (n=14) or IMRT (n=5). The median age at the time of RT was 62.5 months. All children received systemic chemotherapy according to the German Soft Tissue Sarcoma Study protocols (CWS). Patients were grouped classified according to the grouping system used in Intergroup Rhabdomyosarcoma Study Group (IRSG) trials. Patients were immobilized using an individual mask fixation system. For treatment planning contrast-enhanced MRI- and CT-scans were performed. Median size of PTV for RT was 93,4 ml. We applied a median total dose of 45 Gy (range 32 - 54 Gy) using a median fractionation of 5 × 1,8 Gy/week (range 1,6 - 1,8 Gy / week). Deep sedation or general anaesthesia was required for children &lt; 5 years. Results: RT was well tolerated in all children and could be completed without interruptions &gt; 4 days. Minor RT-induced side effects included skin erythema, alopecia, conjunctivitis, mucositis and nausea / vomiting, however no toxicities &gt;CTC grade II developed. The median follow-up time after precision RT was 17 months. Until now, no secondary malignancies developed. After RT, the 3- and 5-year survival rate was 94%. The 3- and 5-year actuarial local control rate after RT was 89%. With respect to tumor localization, the 3- and 5-year local control rates were 100% for patients with RMS of the orbit and 91% for patients with parameningeal tumors. The actuarial freedom of distant metastases rate was 89% at 5 years. For patients with RMS of the orbit only, the actuarial distant progression-free survival rate was 100% at 5 years. The actuarial 3- and 5-year distant metastases-free survival rate was 91%, in children with parameningeal RMS. Conclusions: High precision RT techniques such as IMRT and FSRT offer good coverage of complex shaped target volumes in critical locations with the necessary RT dose while adhering to the tolerance doses of nearby critical normal tissue structures. Local and distant control rates are not reduced. No significant financial relationships to disclose.