tbuckley/cabot-search huggingface dataset:
Clinical and molecular profiling of surgically resected small-cell lung cancer: Intergroup study with FIGHT002 and HOT1301.
Authors: Hiroshi Yokouchi, Hiroshi Nishihara, Takashi Ishida, Hiroyuki Suzuki, Hidetaka Uramoto, Shigeo Yamazaki, Hajime Kikuchi, Kenji Akie, Fumiko Sugaya, Kei Takamura, Masao Harada, Toshiyuki Harada, Mitsunori Higuchi, Yuka Fujita, Makoto Maemondo, Osamu Honjo, Hirotoshi Akita, Hiroshi Isobe, Masaharu Nishimura, Mitsuru Munakata
Journal: Journal of Clinical Oncology (2014)

7590 Background: NCCN and Japanese guidelines suggest surgery for patients with c-stage I small-cell lung cancer (SCLC). However, the clinical impact of surgery with other variables on patients with early-stage SCLC has yet to be determined. Thus clarification of the clinical and molecular profile of SCLC is required. Methods: We reviewed the clinical courses of 149 patients with SCLC who had undergone surgery at 16 institutes from January, 2003 through January, 2013. Eighty-nine paraffin-embedded tissue samples were subjected to immunohistochemistry using 8 antibodies, and to next-generation sequencing system (NGS) using MiSeq and TruSight Tumor Panel (Illumina) loading 26 genes (UMIN registration No. 000010116/10117). Results: Median relapse-free survival (RFS) and overall survival (OS) were 16.6 (95%CI=7.1-26.2), and 36.7 (17.3-56.2) months, respectively. Multivariate analysis revealed that OS was longer in patients without interstitial pneumonitis (IP) (HR=0.372, 95%CI=0.181-0.767, p=0.007), without history of malignancy (HR=0.446, 0.229-0.868, p=0.017), with preoperative diagnosis (HR=0.401, 0.210-0.767, p=0.006), with c-stage II and under (HR=0.204, 0.065-0.640, p=0.006), and with p-stage IA (HR=0.294, 0.142-0.605, p=0.001). Of the 89 patients whose samples were available, MED12 and TGF-βRII were highly expressed in nucleus and cytoplasm, respectively in 92% and 61%. Multivariate analysis demonstrated that high expression of either c-Kit or HER2 in tumors is an independent factor for longer OS (HR=0.396, 95%CI=0.209-0.752, p=0.005). None of the tumors expressed ALK. There was no relationship between the expression of c-Met, EGFR, and VEGFRII and either of RFS or OS. Thirty-five samples were subjected to NGS so far. However, no druggable mutations of BRAF, EGFR, ERBB2, KRAS, KIT, PDGFRA, PIK3CA, FOXL2, GNAQ, GNAS, and FGFR2 were found. Conclusions: These results indicate that i) complication of IP and history of malignancy might be major decision factors of surgery, and: ii) patients with c-stage II should be considered for surgery in a prospective trial. Immunohistochemistry results assist us in gaining a better understanding of the biology of SCLC.
Predicting significance of EGFR mutation existing in tissues and plasma concuurrently or alone to EGFR–tyrosine kinase inhibitors (EGFR-TKIs) for advanced non-small cell lung cancer.
Authors: Yuyan Wang, Jie Wang, Hua Bai, Zhijie Wang, Jianchun Duan, Tongtong An, Jun Zhao, Minglei Zhuo, Meina Wu, Shuhang Wang
Journal: Journal of Clinical Oncology (2013)

e19091 Background: To investigate predicting significance of EGFR mutations existing in tissues couples with plasma or either sample alone to EGFR–tyrosine kinase inhibitors (EGFR-TKIs) treatment for advanced non–small-cell lung cancer (A-NSCLC). Methods: Two hundred-eighty-seven A-NSCLC patients met following criteria were included into this study: 1) had received EGFR-TKIs as first- or second-line therapy; 2) had sufficient tissue and plasma samples for EGFR mutation analysis. All patients were divided into four subgroups which were wild-type EGFR in both of specimens (B - /T - ), mutated in both of specimens (B + /T + ), mutated only in one specimen (B + /T - and B - /T + ). EGFR mutation was screened by denaturing high performance liquid chromatograph (DHPLC) and confirmed by ARMS. Objective response rate (ORR) and progression-free survival (PFS) were compared among four subgroups. Results: Of all 287 patients, 101 patients carried EGFR mutation both in tissue and plasma, 103 patients carried mutation only in tissue (65 cases) or plasma (38 cases). Median PFS was 9.2 months (95% CI, 6.3 to 12.1) and 2.0 months (95% CI, 1.3 to 2.7) in B+/T+ and B-/T- group, respectively. For single mutated group, mPFS were 7.87 month for B-/T+ group (95% CI, 5.1 to 10.6) and 11.87 months for B+/T- group (95% CI, 3.3 to 20.5) (P=0.001). For ORR, 53.0% for B+/T+ group, 15.8% for B-/T- group, 40.0% for B-/T+ group and 28.9% for B+/T- group (P=0.000). EGFR-TKIs therapeutic line could not change trend which B+/T- or B+/T+ group had better PFS than B-/T+ group. Conclusions: Detection of EGFR mutation in tissue and plasma may have different significance in predicting response of EGFR-TKIs.
Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma following first-line therapy with sorafenib: Patient-focused outcome (PFO) results from the phase 3 REACH study.
Authors: Ian Chau, Markus Peck-Radosavljevic, Christophe Borg, Peter Malfertheiner, Jean Francois Seitz, Joon Oh Park, Baek-Yeol Ryoo, Chia-Jui Yen, Masatoshi Kudo, Ronnie Tung-Ping Poon, Davide Pastorelli, Jean-Frédéric Blanc, Hyun Cheol Chung, Ari David Baron, Takuji Okusaka, Zhanglin Lin Cui, Allicia C. Girvan, Paolo Abada, Ling Yang, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2015)

4077 Background: REACH did not demonstrate a significant improvement in overall survival (OS) in the ITT population, but pts in the RAM group with an elevated baseline alpha-fetoprotein (AFP) ≥400ng/mL (pre-specified) had meaningful improvement in OS (HR 0.67, p < 0.05). Here we present PFOs (pt-reported FACT Hepatobiliary Symptom Indexes [FHSI-8] and clinician-reported Eastern Cooperative Oncology Group [ECOG] performance status [PS]) from the REACH study. Methods: Eligible pts had advanced HCC; Child-Pugh A; ECOG PS 0 or 1; and prior sorafenib. Pts were randomized 1:1 to receive RAM (8 mg/kg) or placebo (PBO) on day 1 of an every 2 week cycle. The FHSI-8 was completed at baseline, cycles 4, 10, 16, and end of treatment. PS was assessed at baseline, each cycle, and end of treatment. Time to deterioration (TtD) in FHSI-8 was defined as the time from the randomization date to the first date with a ≥3-point decrease (based on 32-point scale) from baseline. TtD in PS was defined as the time from the randomization date to the first date a change to PS ≥2 was observed. Kaplan-Meier method and Cox regression were used to assess TtD. Results: Compliance with FHSI-8 was balanced between treatment arms. In the ITT population, TtD in FHSI-8 and PS were similar between RAM and PBO. In the elevated AFP population, there was a strong trend toward a delay in the deterioration of symptoms in FHSI-8 (p = 0.054) and PS (p = 0.057) for RAM treated pts compared to PBO. Conclusions: In the ITT population, symptom score and TtD were comparable between treatment arms; RAM did not result in the detriment in symptoms or pt functioning. Delay in symptom and PS deterioration coupled with survival benefit was observed in pts treated with RAM in the elevated AFP population. Clinical trial information: NCT01140347. ITT AFP ≥400 ng/ml RAM PBO RAM PBO FHSI-8 Compliance Baseline, % 96.5 94.7 99.2 94.7 FHSI-8 Compliance End of Treatment, % 62.1 72.5 67.2 76.6 FHSI-8 Score Change from Baseline, mean -2.44 -2.86 -2.21 -3.73 TtD FHSI-8, mo HR (95% CI) 1.04 (0.80-1.34) 0.69 (0.47-1.01) P value 0.78 0.054 TtD ECOG PS ≥2, mo HR (95%CI) 0.89 (0.65-1.22) 0.64 (0.41-1.02) P value 0.47 0.057
Circulating tumor cells (CTCs) detection in a randomized phase II trial of neoadjuvant chemotherapy for large operable and locally advanced breast cancer (REMAGUS 02): Preliminary results
Authors: J. Y. Pierga, C. Mathiot, J. M. Extra, P. Tresca, J. Asselah, B. Sigal-Zafrani, E. Brain, V. Diéras, L. Mignot, M. Marty
Journal: Journal of Clinical Oncology (2006)

10637 Background: The presence of CTCs in blood from metastatic breast cancer patients before first line chemotherapy and persistence of CTCs after initiation of treatment, are predictive of shorter overall survival (Cristofanilli M; et al, 2005, J Clin Oncol 23:1420–1430). CTCs could be used as a surrogate marker. The aim of this study was to determine if CTC were present in the blood of patients who received neoadjuvant chemotherapy (CT) for large operable and locally advanced breast cancer, before initiation of CT (preCT) and at the end of CT before surgery (postCT). Methods: 7.5 ml of blood were obtained on CellSave tube from patients included in an ongoing randomized phase II trial. All patients received 4 cycles of Epirubicin-Cyclophosphamide every 3 weeks followed by 4 cycles of docetaxel associated with or not trastuzumab for HER2 positive patients and with or not celecoxib for HER2 negative patients. CTCs were immunomagnetically separated and fluorescently stained with the CellSearch kit. Cells were classified using the CellSpotter Analyzer as CTCs if they stained positive for DAPI (nuclear dye), and cytokeratin 8, 18 and 19, and if they stained negative for the leucocyte-specific antibody CD45. Results: From 10/2004 to 12/2005, preCT blood samples were obtained in 60 patients, analyzed in 56 for technical reasons. At least one CTC was detected in 15/56 (27%, CI 95%: 15.5–38.5%), 1 to 17 cells per sample (median 1.5). With a threshold of 2 cells, 8/56 (14%, CI 95%: 5–23%) patients were classified positive. At time of analysis, pre CT and post CT samples from the same patient were available for 19 patients. Six had &gt;1 CTC/sample before CT (31.5%) and only one (1/6, 17%) remained positive after CT. Thirteen were negative for CTC before CT and 2/13 (15%) became positive after CT, with only one cell per sample. Conclusions: CTCs can be detected in blood of patients with large operable or locally advanced breast cancer before initiation of neoadjuvant CT and can be monitored during treatment. Longer follow-up and a larger number of patients are expected before correlating these data with tumor response and survival. No significant financial relationships to disclose.
Congenital Undifferentiated Pure Erythroid Leukemia
Authors: Akihiro Tamura, Daiichiro Hasegawa, Suguru Uemura, Atsuro Saito, Emiko Takeoka, Saki Okubo, Nanako Nino, Takehito Yokoi, Teppei Tahara, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Seiji Yoshimoto, Keiichiro Kawasaki, Hideto Nakao, Makiko Yoshida, Naoya Morisada, Yoshiyuki Kosaka
Journal: Blood (2016)
Comparative outcomes of minimally invasive and robotic-assisted esophagectomy.
Authors: Kenneth L Meredith, Jamie Huston, Ravi Shridhar
Journal: Journal of Clinical Oncology (2017)

167 Background: Minimally invasive esophagectomy(MIE) has demonstrated superior outcomes compared to open approaches. The myriad of techniques has precluded the recommendation of a standard approach. The addition of robotics has potential to further improve outcomes. We sought to compare the outcomes of existing techniques for MIE with robotic assisted approaches. Methods: Utilizing a prospective esophagectomy database we identified patients who underwent (MIE) via Ivor Lewis(TT), transhiatal(TH) or robotic assisted Ivor Lewis(RAIL) techniques. Patient demographics, tumor characteristics and complications were analyzed via ANOVA, Chi-Square, and Fisher Exact where appropriate. Results: We identified 302 patients who underwent MIE: TT 95(31.5%), TH 63(20.8%), and RAIL 144(47.7%) with a mean age of 65±9.6. The length of operation was longer in the RAIL: TT(299±87), TH(231±65), RAIL(409±104 minutes), p &lt; 0.001. However the EBL was lower in the RAIL patients: TT(189±188ml), TH(242±380ml), RAIL(155±107ml), p = 0.03. Conversion to open was also lower in the RAIL group: TT 7(7.4%), TH 8(12.7%), RAIL 0, p &lt; 0.001. The R0 resection rate and lymph node (LN) harvest also favored the RAIL cohort :TT 86(93.5%), TH 60(96.8%), and RAIL 144(100%), p = 0.01. LN:TT 14±7, TH 9±6, and RAIL 20±9, p &lt; 0.001. The overall morbidity was lower in RAIL patients: TT 29(30.5%), TH 39(61.9%), RAIL 34(23.6%), p &lt; 0.001. Mortality was lower in the TT and RAIL approaches compared to TH but was not significant: TT 2 (2.1%), TH 2 (3.2%), and RAIL 2 (1.4%), p = 0.6. Conclusions: RAIL demonstrates lower EBL, conversion to open, and morbidity than other MIE techniques. Additionally the oncologic outcomes measured by R0 resections and LN harvest also favored the patients who underwent RAIL.
Phase II study of cixutumumab (IMC-A12) in thymic malignancies.
Authors: Arun Rajan, Gregory J. Riely, Corey Allan Carter, Anish Thomas, Sean Khozin, Isabella Bergagnini, Arlene W Berman, Barbara Scepura, Eva Szabo, Min-Jung Lee, Jane B. Trepel, Sarah K Browne, Minjal J Pancholi, Liang Cao, Helen X. Chen, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2012)

7033 Background: The IGF-1 receptor (IGF-IR) is expressed in thymoma (T) and thymic carcinoma (TC). Prolonged SD has been seen with anti-IGF-IR therapy in thymic tumors in phase I trials. Cixutumumab (C) is a fully human IgG1 monoclonal antibody (ab) that targets IGF-IR. Methods: Patients (pts) with recurrent T or TC, PS 0-2, measurable disease, and normal organ function received C at 20 mg/kg IV q3wks until progression or intolerable toxicity. Primary endpoint was response rate. Correlative studies included immune cell subset (central memory, effector memory, naïve and regulatory T cells), circulating endothelial progenitor (CEP) cell, serum IGF-1 and IGF-IR in PBMCs, anticytokine ab, and tumor mutational analysis. Results: Forty-five pts enrolled from two centers (20 female, T=33, med age 52 yrs, range, 26-86). Median number of prior systemic treatments: 3 (range, 1-11). Median number of cycles of C administered: 6 (range, 1-41). In 30 evaluable T pts there were 4 (13%) PR, 23 (77%) SD, and 3 (10%) PD. Corresponding numbers in 12 TC pts were 0, 5 (42%) and 7 (58%). Median PFS for T and TC was 40 and 9 wks respectively. C-related grade 3/4 AEs were hyperglycemia (8%), hyperuricemia, weight loss, lipase elevation, chest wall pain (5% each) and AST elevation (3%). Two pts died while on study: one due to respiratory insufficiency related to T after 5 cycles and one due to worsening myasthenia and an acute coronary event after 13 cycles. In 8 of 33 T pts autoimmune (AI) symptoms developed (4 new-onset) due to immune thrombocytopenic purpura, myositis, myocarditis, colitis, PRCA and food allergy. In the first 13 pts a trend towards increased numbers of central and effector memory T cells and a decrease in naïve T cells and CEPs was seen. High-titer anticytokine abs, including anti-IFNa, anti-IL-12, and anti-IL-17A, were found in 13/27 pts tested. No EGFR, KRAS or BRAF mutation, HER2 amplification or ALK translocations were detected in 11 tumors analyzed. Conclusions: C monotherapy is well tolerated and active in T. Accrual will continue until 37 T pts are enrolled. Activity in TC is unworthy of further investigation. CEP and immune cell subset analysis suggests therapy may impact angiogenesis and immune response. Development of AI symptoms during treatment needs further evaluation.
Baseline predictors of early treatment failure in patients with platinum resistant/refractory (PRR) and potentially platinum sensitive (PPS ≥ 3) recurrent ovarian cancer (ROC) receiving ≥ 3 lines of chemotherapy: The Gynaecologic Cancer Intergroup (GCIG) Symptom Benefit Study (SBS).
Authors: Felicia T Roncolato, Rachel O'Connell, Florence Joly, Anne Lanceley, Felix Hilpert, Aikou Okamoto, Eriko Aotani, Sandro Pignata, Paul P. Donnellan, Amit M. Oza, Elisabeth Avall-Lundqvist, Jonathan S. Berek, Katrin Marie Sjoquist, Kim Gillies, Phyllis Butow, Martin R. Stockler, Madeleine Trudy King, Michael Friedlander
Journal: Journal of Clinical Oncology (2015)

5564 Background: Women with PRR/PPS ≥ 3 ROC are a heterogeneous group with unpredictable response to palliative chemotherapy (PC). GCIG SBS recently completed recruitment of 949 patients treated with PC. Primary aim is to validate an instrument to measure symptom benefit; secondary aims include identifying factors that predict early progression. 25% of patients with PRR-ROC received < 8 weeks of PC. Methods: Physicians recorded baseline characteristics, symptoms (symptomatic ascites, cramping abdominal pain), site/extent of disease and prespecified lab values. Association between baseline characteristics and progression-free survival (PFS) was assessed using time-to-event methods. Median PFS was calculated according to clinically relevant categories and log-rank test applied to assess prognostic value. Cox regression was used to compute hazard ratios and 95% CI to assess the effect of variables on PFS. Results: Sufficient follow up for analysis of PFS was available in 791 patients. Median PFS and overall survival were 4.3 (95% CI: 3.9-4.9) and 12.9 months (95% CI: 11.4-14.0) respectively. In univariate analysis factors with statistically significant associations with PFS included: haemoglobin, PRR-ROC, ascites and abdominal cramps, nodal disease, thrombocytosis, CA125 > 1000, LDH > 600, ECOG status, and elevated c reactive protein. Non-significant factors included: visceral metastases, albumin < 25, lymphocytes < 0.5, tumour volume. Significant variables in multivariable analysis included: ECOG ≥ 2 (HR 1.61 95% CI 1.18-2.19 p = 0.003); nodal disease (HR 1.37 95%CI 1.13-1.67 p = 0.002); ascites (HR 1.54 95%CI 1.24-1.92 p = 0.0001); platinum resistant vs. sensitive (HR 1.39 95%CI 1.12-1.72 p = 0.002), CA125 > 1000 (HR 1.35 95%CI 1.09-1.67 p = 0.005); LDH > 600 (HR 1.88 95%CI 1.36-2.60 p = 0.0001). Conclusions: Several simple clinical variables help predict patients who progress rapidly and will be used to construct prognostic models to aid clinical decisions and trial stratification for clinical trials in PRR/PPS ≥ 3 ROC Clinical trial information: 12607000603415.
When using patient-reported outcomes in clinical practice, the measure matters: Results from an RCT.
Authors: Claire Frances Snyder, Joseph M. Herman, Amanda L. Blackford, Michael Anthony Carducci, Albert W. Wu
Journal: Journal of Clinical Oncology (2013)

6519 Background: Patient-reported outcomes (PRO) assess patients' perspectives on the impact of diseases and treatments. There is increasing interest in having patients complete PRO questionnaires and using the data clinically to identify and address patients' issues. There are many different PRO questionnaires, and this study investigated whether one PRO is more appropriate than others for clinical use. Methods: This controlled trial randomly assigned patients to complete 1 of 3 PRO questionnaires: six domains from the Patient Reported Outcomes Measurement Information System (PROMIS), the EORTC QLQ-C30, or the Supportive Care Needs Survey-Short Form (SCNS). Breast or prostate cancer patients, &gt;=21 years old, undergoing treatment, with oncologist visits at least monthly were eligible. Patients completed their assigned PRO questionnaire via computer either in the clinic or via the web prior to their clinic visits for the duration of active treatment. The results were provided to their clinicians for use during visits. After treatment ended, patients completed a 13-item feedback form to assess the impact of the questionnaire on their care (e.g., easy to complete, promoted communication, improved care quality). We hypothesized that there would be no difference in the proportion of patients who strongly agreed/agreed to all 13 items in the feedback form by questionnaire arm. Results: Of 294 eligible patients approached, 224(76%) enrolled (mean age 66, 78% white, 28% breast, 72% prostate). Of these, 181 patients (81%) responded to the feedback form, with 116 patients (52%) completing all 13 items. Of the 116 patients with complete data, subjects in the QLQ-C30 arm were most likely to strongly agree/agree to all items (82%), followed by PROMIS (62%), and SCNS (56%) [p=.05]. Among the 181 patients with at least partial data, the proportions strongly agreeing/agreeing to all items were 74% for QLQ-C30, 61% for PROMIS, and 52% for SCNS [p=.03]. Conclusions: In a randomized trial comparing the benefits of PROs applied in clinical practice, we found significant differences among the 3 PRO questionnaires. Future applications of PROs for patient care should select the most appropriate PRO measures for the purpose and setting.
Initial experience with sipuleucel-T (sip-T) in the immediate post-approval setting: The University of Washington (UW) experience.
Authors: James P. Dean, Evan Y. Yu, Suzanne Beauchene, Suzanne P Hall, Celestia S. Higano
Journal: Journal of Clinical Oncology (2012)

e15206 Background: UW has participated in clinical trials of sip-T for over 15 years. After sip-T administration in the 3 phase III trials, patients (pts) did not receive additional therapy until objective progression. However, the course of treatment after administration of sip-T outside the setting of a clinical trial is not defined. In order to better understand our own practices in response to this new clinical scenario, we evaluated our institutional experience with commercial sip-T after FDA approval. Methods: Charts of all pts treated with sip-T at UW with at least 3 mos follow-up were retrospectively reviewed. Pt characteristics and treatments administered during the first 3 mos after sip-T infusion were collected. The institutional review board approved this study. Results: Between June 2010 and Nov 2011, 36 pts with mCRPC were treated with commercial sip-T by 3 different MDs. There were 31 Caucasian, 3 African American, and 2 Asian pts. At diagnosis, Gleason score (# pts) was 3+3 (2), 3+4 (5), 4+3 (7), 4+4 (4), 4+5 (16), 5+5 (2); initial therapy was watchful waiting (1), ADT with brachytherapy [BT] (1), BT with XRT (4), ADT/XRT (6), radical prostatectomy [RP] (9), ADT/RP (1). At the time of sip-T therapy, median age 67.8 yrs (44.2 to 84.5), median PSA 56.0, LDH 179.5, alk phos 77, Hgb 12.7, CTC 2. 3 pts had prior chemotherapy for metastatic disease. 34, 2, and 1 pts received 3, 2, and 1 sip-T infusion(s) respectively. Within the first 3 mos after the last sip-T dose, 29 pts had no significant symptoms and received no additional therapy other than ADT +/- ongoing zoledronic acid or denosumab (27), ketoconazole (1), or nilutamide (1); 7 developed pain and received docetaxel [D] (1), XRT and D (3), XRT (1), nilutatmide/D (1), or cabozantinib (1). 6 pts died a median of 10 months after sip-T; none had received chemotherapy before sip-T therapy. Conclusions: The majority of UW pts (80%) received no additional therapy in the first 3 mos after sip-T while 20% developed pain and were treated with docetaxel or other systemic therapy. What treatments should be given and at what interval after sip-T remains unclear. It is likely that new agents will impact the treatment paradigm after sip-T.