tbuckley/cabot-search huggingface dataset:
A phase II study of elacytarabine plus idarubicin as second course remission-induction therapy in patients with acute myeloid leukemia.
Authors: D. Rizzieri, U. Krug, R. F. Schlenk, N. Vey, X. G. Thomas, F. Huguet, M. Johansen, T. F. Jacobsen
Journal: Journal of Clinical Oncology (2011)

TPS207 Background: Elacytarabine is a fatty acid derivative (elaidic acid ester) of the antimetabolite cytarabine,which is widely used in the treatment of AML. Preclinical data has shown that the entry of cytarabine into tumour cells is dependent on the expression of specific membrane transporter proteins, particularly of hENT1 (human equilibrative nucleoside transporter 1). Decreased expression of hENT1 is a major factor in cytarabine resistance in childhood AML (Hubeek et al., 2005). For entry into cells elacytarabine is independent from transporters and offers therefore an opportunity for treating patients not likely to benefit from cytarabine. In phase I studies activity of elacytarabine has been observed in patients with refractory/relapsed AML, as monotherapy as well as in combination with idarubicin. Synergy has been observed for the combination elacytarabine and anthracycline in vitro, and in phase I the combination has demonstrated a safety profile similar to cytarabine and idarubicin. Methods: Patients with AML who have failed their first remission-induction course of a cytarabine based combination will be treated with elacytarabine in combination with idarubicin. The study is ongoing and will recruit up to 50 patients at 10 sites in the USA and Europe. As of 28th January, 8 sites are activated and 16 patients have been enrolled. The objective of the study is to determine response rates to the combination treatment and to evaluate by immunohistochemistry the hENT1 status of AML cells. The hENT1 expression level will be analysed at time of diagnosis and/or before elacytarabine treatment. The goal is to explore the relationship between response to cytarabine and to elacytarabine and the AML hENT1 status. Key Inclusion Criteria: Patients with AML who have received one previous cytarabine containing regimen and who have more than 5 % remaining blasts in the bone marrow following the first induction course. Bone marrow sample will be collected for the determination of the hENT1 expression level prior to treatment in the protocol. Patients must be 18 years of age or older and have an ECOG performance status of 0 – 2.
Quality of radiation therapy referral and utilization post-prostatectomy: A population-based study of time trends.
Authors: Chunzi Jenny Jin, Michael Donald Brundage, Earl Francis Cook, Qun Miao, Timothy P Hanna
Journal: Journal of Clinical Oncology (2016)

286 Background: Adjuvant radiotherapy (ART) post-radical prostatectomy (RP) has been shown to benefit patients with pathologic T3 or margin-positive prostate cancer. It remains unclear whether early salvage radiotherapy (SRT) confers equivalent outcomes to ART. Practice Guidelines recommend referral to radiation oncology (RO) within 6 months of RP to discuss ART and SRT. The study objectives were to (1) assess post-RP referral patterns to RO; (2) describe ART and SRT utilization; and (3) compare time trends before and after seminal trials and guidelines were published. These provide indications of access to quality care. Methods: This was a retrospective cohort study. Electronic clinic visit and RT treatment records were linked to the population-based Ontario Cancer Registry. The study population included all prostate cancer cases treated with RP in Ontario January 1, 2003 - November 30, 2012. ART was defined as curative RT within 6 months of RP, and SRT was 6 - 24 months post-RP. Changes in RO referral and RT rates over time were statistically analyzed using the Cochran-Mantel-Haenszel Chi-Square test. Results: Over the study period, 30,447 prostate cancer patients received RP and 15.2% saw an RO within 6 months of RP. This proportion doubled between 2003 and 2012 (from 10.7% in 2003-2004 to 21.7% in 2011-2012, p &lt; 0.001 for trend). The annual percentage change was largest 2009-2011 (3.4%). In comparison, the proportion seen within 24 months of RP remained stable at 32.3% ± 1.4%. Amongst the 4,641 patients seen by an RO within 6 months of RP for consideration of ART or SRT, the proportion receiving ART remained relatively constant at 51.0% ± 3.0%. Commensurate with RO referral trends, there was a doubling in ART rates amongst all RP cases, ranging from 5.4% in 2003-2004 to 11.0% in 2011-2012 (p &lt; 0.001), compared to relatively stable SRT rates of 8.5% ± 0.2% (7.9% in 2003-2004, 8.9% in 2010-2011). Consequently, the total proportion receiving RT within 24 months of RP increased from 14.1% in 2003-2004 to 19.8% in 2010-2011 (p &lt; 0.0001). Conclusions: There was an increase in access to early RO referral post-RP and in ART utilization in Ontario from 2003 to 2012, following publication of key clinical trials and guidelines.
Fluoropyrimidine/platinum-based first-line chemotherapy in metastatic esophageal squamous cell carcinoma: Prognostic factor analysis in 239 patients.
Authors: H. A. Jung, J. Lee, H. K. Ahn, S. H. Park, Y. H. Park, Y. Im
Journal: Journal of Clinical Oncology (2011)

4088 Background: Esophageal squamous cell carcinoma (SCC) is considerably more prevalent in East Asia. Despite of relatively high prevalence of esophageal SCC, prognosis is very poor with limited options of effective chemotherapy regimens. We attempted to identify favorable subgroups of patient who are likely to benefit from 5-fluorouracil/cisplatin (FP) or capecitabine/cisplatin (XP) chemotherapy as first-line treatment. Methods: Between January 2000 to December 2010, 239 patients were diagnosed of recurrent, metastatic esophageal SCC and received either FP or XP as first-line chemotherapy. Clinicopathologic variables and treatment outcome were retrospectively collected. Results: Among 239 patients, 104 (43.5%) patients had recurrent esophageal SCC after previous curative resection (n=93) or definitive concurrent chemoradiotherapy (n=11), and 135 (56.5%) patients had metastatic disease at initial diagnosis. 143 (59.8%) patients received FP and 96 (40.2%) patients received XP. There was no difference in response rate (RR) between FP group (RR=44.8%) and XP group (RR=54.2%; p=0.154). Median progression-free survival (PFS) and median overall survival following FP/XP chemotherapy for 239 patients were 4.4 months (95% CI, 3.954-4.786) and 11.3 months (95% CI, 9.837-12.763), respectively. There was no difference in OS and PFS between the two regimen groups. At multivariate analysis, poor performance status (ECOG≥2), low albumin level (≤3.5g/dL), and weight loss (10% of the weight loss for 3 months) at the time of chemotherapy were significantly associated with both worse PFS (P<0.05) and OS (P<0.05). When patients were categorized into risk groups according to risk score (1=one factor), median OS for each subgroup (0, 1, 2-3) was 14.7 months (95% CI, 10.507-18.953, n=104), 10.3 months (95% CI, 8.680-11.860, n=90), and 5.9 months (95% CI, 3.047-8.753, n=39) respectively (P<0.001). Conclusions: The present study represents the largest series to analyze the treatment outcome of FP/XP chemotherapy in metastatic SCC. Risk-adapted stratification of treatment for subgroup of metastatic SCC patients should be actively pursued.
The effect of chemotherapy on overall survival of stage II colon cancer.
Authors: M. Omaira, M. Mozayen, K. Katato
Journal: Journal of Clinical Oncology (2011)

625 Background: Surgical resection of local colon cancer is the only curative treatment, at the same time adjuvant chemotherapy is clearly shown to be beneficial as the standard of care for node positive disease (stage III) colon cancer. However the role of chemotherapy for stage II colon cancer treatment is still conflicting. We aim to compare the overall survival rate of stage II colon cancer patient's with and without chemotherapy. Methods: A retrospective observational study was conducted from 1990-2006. Patients with stage II colon cancer were included. Patient's characteristics including age, gender, common site of involvement, histology patterns, overall survival rate and treatment with chemotherapy were recorded. Results: A total of 138 consecutive patients were identified from 1990-2006. The median age was 68 (21-91) year, males (44%), African Americans (47.6%). The most common sites of the primary tumor were sigmoid and cecum (22.4%) each. Adenocarcinoma being the most common pathology. Majority of the patients (86.2%) were found to have T 3 tumors. Of the patients that received chemotherapy (29/44) 66% had an overall survival rate of three years or more, whereas (53/94) 57% of the patients who did not receive chemotherapy had a survival rate of three years or more. The difference of survival rates between the two groups of patients was not statistically significant. Conclusions: The role of chemotherapy in stage II colon ancer is still controversial. There was no significant difference in overall survival between the two groups who did and did not receive chemotherapy; thus more studies are warranted to explore the factors that predict the survival of stage II colon cancer. No significant financial relationships to disclose.
Association of <i>GSTP1</i> hypermethylation with reduced protein expression and its correlation with clinical stage in neuroblastoma.
Authors: F. Gumy-Pause, B. Pardo, M. Khoshbeen-Boudal, M. Ansari, E. F. Attiyeh, H. Ozsahin
Journal: Journal of Clinical Oncology (2011)

9537 Background: Neuroblastoma (NB) is the most common malignant disease of infancy and accounts for approximately 8% of all childhood cancers. The clinical hallmark of this tumour is the marked variability in prognosis depending of the age, stage and biological characteristics. Aberrant methylation of CpG-islands has been shown to be associated with transcriptional inactivation of tumor suppressor genes in a wide spectrum of human cancers. The aim of this project was to determine the methylation status of 35 different genes in NB cell lines and primary NB tumors (NBT). Methods: Sixteen NB cell lines and 50 NBT were analyzed. We determined methylation status of 35 different gene promoters, using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA, ME001B and ME002 tumors suppressor kits) assay. GSTP1 mRNA and protein expressions were analyzed by qRT-PCR and Western Blot in 4 GSTP1 hypermethylated cell lines and 7 cell lines without hypermethylation. Clinical and biological data are available for the 50 NBT. Results: Ten genes were found hypermethylated in NB cell lines and in NBT: RASSF1 (100%/96%), CASP8 (94%/88%), CD44 (69%/8%), ESR1 (50%/4%), GSTP1 (44%/8%), MGMT (38%/8%), PAX5 (31%/6%), TIMP3 (25%/24%); CDH13 (13%/8%) and IGSF4 (6%/2%), respectively. GSTP1 mRNA and GSTP1 protein levels were found significantly decreased in GSTP1 hypermethylated cell lines vs cell lines without hypermethylation (0.21 vs 1.26; p<0.0005, and 0.22 vs 1.44; p<0.0002, respectively). GSTP1 hypermethylation was found more prevalent in stage 4 vs. stages 1, 2, 3 NBT (4/24 vs. 0/26); p=0.046). All the GSTP1 methylated samples were 11q-deleted, non-MYCN amplified NBT. Conclusions: Our results confirm that epigenetic aberration is frequent in NB. For 5 of these genes, aberrant methylation of CpG-islands in NB was not (PAX5, ESR1 and IGSF4) or very rarely (CDH13 and GSTP1) reported. In NB cell lines, GSTP1 hypermethylation was found correlated with a significant decrease of GSTP1 mRNA and protein expressions. As already reported in various adult cancers, clinical data suggest that epigenetic silencing of GSTP1 gene could be associated to aggressive behavior in NB.
Phase II single-arm, single-institution trial of neoadjuvant gemcitabine and oxaliplatin treatment (NT) in patients (pts) with resectable pancreas adenocarcinoma (PC).
Authors: E. M. O'Reilly, W. R. Jarnagin, M. F. Brennan, C. Winston, L. H. Tang, M. Capanu, M. Schattner, L. Y. Chen, R. P. DeMatteo, C. J. DiMaio, M. I. D'Angelica, R. C. Kurtz, D. S. Klimstra, M. A. Lowery, D. G. Coit, D. L. Reidy, P. J. Allen
Journal: Journal of Clinical Oncology (2011)

4065 Background: Metastases occurs in > 85% resected PC and ~25% will not receive systemic therapy due to postoperative morbidity. NT offers higher likelihood of systemic therapy delivery to all Pts. We conducted a single institution (MSKCC), phase II trial of NT in Pts with resectable PC to assess 18-month survival rate. Methods: Eligibility: radiographically resectable PC, ECOG 0-1. Resectability adjudicated by multidisciplinary team. Borderline resectable Pts ineligible. Prior to NT, all had a CT pancreas angiogram, laparoscopy, research core biopsy (RCB) for xenograft implantation (if feasible). NT: 4 cycles of gemcitabine 1,000mg/m2/100mins and oxaliplatin 80mg/m2/120mins, q2 weeks before surgery. Following R0/R1 resection, 5 cycles of adjuvant gemcitabine were given. Biostatistics: 18-month survival from MSKCC database for resected PC (CT angiogram, laparoscopic staging): 53%. NT promising if 18-month survival was ≥ 73%, type I, II errors = 10%. Planned enrolment of N= 37. Secondary endpoints: response to NT, sites of failure, toxicity, overall survival. Correlative: pathologic RR (pRR) to NT, proteomic analyses, feasibility of obtaining RCB. Results: From 1/08-1/11, N= 45 screened: 34 staged with potentially resectable PC and received NT. Median age: 70 yrs. ECOG 0/1: 29%/71%. M/F: 62%/38%. Head (n= 26), body (n= 4), tail (n= 4). N= 24 R0/R1 resection: 18 R0, 6 R1. Unresectable n= 7: distal progression (n= 2), T4 artery/vein (n= 4), portal hypertension (n= 1). N= 2 grade 5 events, cardiac/CVA pre-surgery. pRR: 0-50%, n= 21; >50%, n= 3. NT gd 3-4 toxicities: hyperglycemia (n= 16), biliary stent (n= 5), hematologic (n= 14), infusion reactions (n= 2). Current disposition: 1 NT, 15 free of recurrence, 4 alive with disease, 14 dead of disease. RCB obtained n= 7 and successful xenograft in n= 4. 18-month survival pending (mature by 05/11). Conclusions: Delivery of NT for resectable PC is feasible, well-tolerated and requires multidisciplinary collaboration. RCB obtainable in body/tail PC. Analysis of primary endpoint will be presented. It remains to be seen whether NT for resectable PC is a superior approach to immediate resection.
Impact of KRAS on outcomes of patients with unresectable colorectal liver metastases (CRLM).
Authors: Celina Ang, Alexandra N. Gewirtz, Joanne F. Chou, Marinela Capanu, Efsevia Vakiani, Nancy E. Kemeny
Journal: Journal of Clinical Oncology (2014)

510 Background: In patients with resected CRLM, mutant (MUT) KRAS may confer a worse prognosis than wild-type (WT) KRAS (Karagkounis et al., ASCO 2012, abs 3616; Kemeny et al., ASCO 2013, abs 3609). We analyzed the impact of KRAS on the outcomes of patients with unresectable CRLM treated with hepatic arterial infusion (HAI) + systemic chemotherapy. Methods: Median overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan Meier methods. The log rank test was used to examine the association of patient demographics and disease-related factors including KRAS mutation status with OS and PFS. Cox proportion hazards model was used to examine the association of liver resection with survival outcomes by treating liver resection as a time dependent covariate. Results: Of 93 patients: 59 male, 34 female; 77 Caucasian, 16 non-Caucasian; 66 were age &lt; 60 years, 27 were age &gt; 60 years; 70 were KRAS WT and 23 were KRAS MUT; 59 had chemotherapy pre-HAI pump placement and 53 subsequently underwent liver resection. Median PFS and OS were 13.3 months and 45.7 months, respectively. Age, sex and race were not associated with PFS or OS. Univariate analysis of the impact of KRAS, pre-HAI chemotherapy, and subsequent liver resection on PFS and OS is presented in the Table. Multivariate analysis including important variables did not change outcome. Conclusions: In patients with unresectable CRLM treated with HAI and systemic chemotherapy, overall survival tended to be improved in KRAS WT vs MUT patients. [Table: see text]
Patients’ experience and physicians strategies for selection of anthracyclines and taxanes sequential treatment in adjuvant breast cancer: The Violayne prospective multicenter survey.
Authors: M. Namer, J. Gligorov, E. Antoine, M. Spielmann, T. Facchini
Journal: Journal of Clinical Oncology (2011)

e19620 Background: Anthracyclines (A) and taxanes (T) are the most prescribed chemotherapy in adjuvant breast cancer (ABC) but can impair quality of life (QoL). Among T paclitaxel (P) and docetaxel (D) could be used with different schedules and toxicity profile. The Violayne survey was conducted to try to understand patients (Pt) and physicians (MD) experience with A and T according to P or D choice. Methods: Violayne was a multicentric French survey conducted prospectively from 2007 to 2010 among 207 Pt. The main inclusion criteria was ABC Pt who completed 3 cycles of A regimen (without T). MD and Pt answered each two questionnaires (end of A and T treatment) and adverse events were collected during the inclusion at the study. QoL auto questionnaires were used for Pt after A and during T treatments. Results: Before inclusion, 82% (n=169) of patients had received epirubicin (FEC protocol: 62%) and 18% (n=38) doxorubicin (AC protocol: 89%). Pt in whom MD prescribed P were those who reported more appetite loss (p<0.0001), nausea/vomiting (p<0.0001), mucosa ulcerations, stomatitis, neutropenia, leucopenia and anemia at the end of A treatment. Those in whom D was preferred were those who reported more dyspnea (p=0.001) or financial problems (p=0.005). Among the fully evaluable Pt, 52% described bad or very bad experience with A. In terms of global health and social functioning, patients’ experience was significantly better with T than with A (p=0.01 for both). Forty-eight of these Pt were treated by P and 82 with D. MD declared that they preferentially choose P for Pt presenting bad tolerance of the A sequence (p=0.002) and for older Pt (p<0.0001). P patients declare a mean of 8.5 ± 4.5 undesirable side effect vs 11.3 ± 4.4 in the D group (p=0.0004). Conclusions: MD consider that P’s tolerance is better than D’s, and this belief drives their T choice following treatment with A.
Next Generation Sequencing (NGS) to reveal mutations in IDH1 and its effect on patient (pt) outcomes in advanced biliary tract cancer (aBTC) who received gemcitabine and cisplatin (GC).
Authors: Daniel H. Ahn, Chul Ahn, Apurva Jain, Sameh Mikhail, Christina Sing-Ying Wu, Richard M. Goldberg, Kristen Keon Ciombor, Anne M. Noonan, Priyanka Sadavartia, Rachna T. Shroff, Milind M. Javle, James Lin Chen, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2016)

287 Background: aBTC is uncommon and has a dismal prognosis with limited therapeutic options. First-line therapy for untreated aBTC is GC, with no approved therapies in the refractory setting. To assess for tumor-specific genetic variants that affect outcomes in patients (pts) who received GC in aBTC, we performed NGS in pts treated with who received GC as first-line therapy. Methods: Archival formalin-fixed, paraffin-embedded samples from pts with mBTC from Ohio State University and MD Anderson Cancer Center who received GC in the first-line and underwent NGS as part of routine care. 315 cancer-related genes plus select introns from 28 genes altered in solid tumors were included in the NGS panel. Univariate Cox regression model was used to determine the association between gene mutations with progression free survival (PFS) and (OS). Results: 80 evaluable pts with aBTC treated with first-line GC chemotherapy underwent successful genomic profiling. A total of 414 cancer-specific mutations were identified, where 49 (12%) genes had mutations with &gt; 5% frequency. 17 of the 49 were known mutations. From the comprehensive analysis, somatic mutations in IDH1 (11 of 80 pts; 13%) (HR 0.31; p = 0.035) was associated with improved overall survival (OS) and progression free survival (PFS). Pts wild type for IDH1 had a median OS of 17.7 months and PFS of 4.5 months, while those with an IDH1 mutation had a median OS that was not reached and an improved PFS of 5.7 months. Conclusions: Somatic mutations in IDH1 were associated with improved clinical outcomes in pts with aBTC who received GC as first-line therapy which is consistent with other solid tumor malignancies. IDH1 is a therapeutic target of interest, where future prospective studies will be necessary to validate the predictive utility and its relevance in pt outcomes in aBTC.
Population Pharmacokinetic (PK) Modeling of Hydroxyurea for Therapeutic Drug Monitoring Applications in Children and Adolescents with Sickle Cell Disease
Authors: Pawel Wiczling, Robert I. Liem, Julie A. Panepinto, Uttam Garg, Susan M. Abdel-Rahman, Gregory L Kearns, Kathleen A Neville
Journal: Blood (2011)
Randomized phase III adjuvant study in high-risk cervical cancer: Simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): A NOGGO-AGO-Intergroup Study.
Authors: J. Sehouli, J. U. Blohmer, S. Kuemmel, I. B. Runnebaum, W. Hartmann, R. Richter, A. Belau, H. Leber, M. Kaufmann, W. Lichtenegger
Journal: Journal of Clinical Oncology (2010)

5005 Background: Adjuvant platinum based radiochemotherapy in high-risk cervical cancer is an established treatment strategy to improve overall survival. Based on several trials for primary and recurrent cervical cancer, the introduction of paclitaxel and carboplatin offers further advantages regarding tumor control and toxicity. Methods: An open-labeled randomized phase III was conducted to compare simultaneous radiochemotherapy with weekly cisplatin (40 mg/m2/w) versus 4 cycles of paclitaxel (175 mg/m2) plus carboplatin (AUC 5) three weekly followed by radiation (50.4 Gy). Inclusion criteria were: stage Ib-IIb after radical hysterectomy and lymph node dissection. High-risk cervical cancer was defined as pN1, L1; V1; adenocarcinoma; > pT1b1. Progression free survival was defined as primary objective. Results: Overall, 271 patients were randomized and 265 were eligible for evaluation, 132 in the S-RC arm and 133 in the PC-R arm. Baseline patient characteristics were not significant different between the two arms. Estimated 2-years progression-free survival was with 82.2% (95%CI: 75.1-89.3) in the S-RC arm vs. 88.0% (95%CI: 82.1-93.9) in the PC-R arm not significant different (p = 0.126). 5-year survival rate was 85.8 % (95%CI) in the PC-R group and thus higher than in the S-RC group (78.9%, 95%CI: 70.2-87.4). This difference did not reach a statistical significance (p = 0.251). Hematological grade 3/4 toxicity was higher in the S-RC group compared to the PC-R group. Alopecia (89.5 vs. 27.9%, p < 0.001) and neurotoxicity (65.9 vs. 15.6%, p < 0.001) were significantly higher in the PC-R arm. Early treatment termination was more frequent in the S-RC arm than in the PC-R arm (31.8% vs. 15.0%, p = 0.001). Conclusions: Despite the fact that a survival benefit could not be achieved by the experimental regimen, toxicity profile and tolerability favor the use of a sequential strategy of systemic chemotherapy followed by radiation in high-risk cervical cancer. No significant financial relationships to disclose.