tbuckley/cabot-search huggingface dataset:
Integrative and multidisciplinary clinical trial using imaging, molecular, and dynamic biomarkers to predict bevacizumab plus chemotherapy response in breast cancer.
Authors: J. M. Lopez-Vega, E. G. Calvo, A. Plazaola, B. Hernando, S. Morales Murillo, A. Anton, R. M. S. Gomez, I. Alvarez, J. J. Illarramendi, A. De Juan, P. Martinez, A. Llombart, S. J. Scherer, L. Sabariz, A. la Huerta, L. J. Pina, I. Dominguez, M. J. Garcia Velloso, V. Boni, J. Garcia-Foncillas
Journal: Journal of Clinical Oncology (2011)

TPS153 Background: Despite several investigations, currently there are no proven biomarkers of bevacizumab efficacy. These studies are in advanced cancers and types of biomarkers and/or time points investigated are often limited. To determine the mechanisms of response and identify pathological characteristics of breast cancer (BC) patients (pts) most likely to be benefited of bevacizumab therapy, we choose a neoadjuvant setting where response could be examined as pathological response and where likely mechanisms of resistance are not yet developed. Multiple dynamic biomarkers are analyzed to best characterize tumors and combined to make robust predictions. Methods: This is a multicenter, phase II, non randomized study. Ethical approval was obtained in June 2009. Enrolment of 72 pts in the training set and 160 in the validation set is expected. Eligibility criteria are: women with age ≥18 years, performance status 0-1, histologically proven, previously untreated and stage II-III BC, adequate bone marrow, renal and liver functions. Pts receive single infusion of bevacizumab (15 mg/kg) (C1) 3 weeks prior chemotherapy consisting in 4 cycles of docetaxel (60 mg/mq), adriamicine (50 mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5). Pts undergo surgery and tumor pathological response is evaluated. Imaging assessments include Dynamic Contrast-Enhanced (DCE-MRI), FLT and MISO PET-CT. Core biopsies for gene array, miRNA profiling and immunohistochemistry analysis are performed. Blood samples are collected in EDTA for studying circulating antiangiogenic factors in plasma and single nucleotide polymorphisms in germline DNA. Each assay is performed at baseline, after C1 and C5. Primary endpoints are to identify pathways regulating early antiangiogenic response and to correlate these biomarkers with pathological response. Second endpoints are to determine the efficacy and feasibility of the therapy in this setting. The study is ongoing, enrolment of training set has been completed but pathological response is currently not available.
A multi-analyte assay for the noninvasive detection of bladder cancer.
Authors: Makito Miyake, Steve Goodison, Myron Chang, Yunfeng Dai, Virginia Urquidi, Charles Joel Rosser
Journal: Journal of Clinical Oncology (2013)

306 Background: Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. Methods: We performed a case-controlled validation study in which voided urines from 550 patients (220 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9,MMP-10, SDC1,CCL18, PAI-1, CD44, VEGF, ANG, CA9,A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. Results: An 3-biomarker model (CA9, PAI-1 and IL-8) achieved the most accurate BCa diagnosis (sensitivity 90%, specificity 88%). These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Conclusions: Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.
Rh-endostatin Injection plus paclitaxel and carboplatin therapy for non-small-cell lung cancer: Randomized, double-blind, placebo-controlled, multicentre study
Authors: B. Han, Q. Xiu, H. Wang, Y. Luo, Z. Zhuang, X. Jin
Journal: Journal of Clinical Oncology (2008)

19126 Background: Patients with non-small cell lung cancer are currently treated with concomitant or sequential chemotherapy and radiotherapy. However, the effect of existing treatment modalities is unsatisfactory. Progress of new strategies including more efficient therapy is warranted. Endostar (Rh-endostatin Injection) may have anti-tumor activity by against vascular endothelial growth factor for initial treatment. This study was designed to evaluate the security and the validity of the combination endostatin-paclitaxel and carboplatin (TC) therapy in patients with nonsmall-cell lung cancer (NSCLC) seeking for the more effective method of treatment. Methods: In this randomized, double-blind, placebo-controlled, multicentre trial, 126 patients between July 5 2007 and June 30 2008 are planned to enroll in randomized into 2 groups from 10 centers: the experimental group and control group (1:1). The code-breaking time estimate is about June 2009. The leader units are Shanghai Chest Hospital Affiliated to Shanghai Jiao-Tong University and Shanghai Changzheng Hospital. Main eligibility criteria were histologically or cytologically proven stage III or IV NSCLC, with an age of 18–75 years. All eligible patients received 1 cycle (21 days) of TC chemotherapy. After chemotherapy, patients with the curative effect reaches above SD or SD were randomized to receive endostar plus TC or TC alone for 3 cycles. Each 21-day cycle consisted of endostar 7.5mg/m2 on days 8 to days 21, carboplatin AUC 5 on day 1, and paclitaxel 175 mg/m on day 1. Primary evaluating indicator: time to progression (TTP), 1 year, 2 years and 3 year survival rate. Secondary evaluating indicator: the response rate (RR), mean survival time (MST), quality of life (QOL) and adverse reaction in the treatment, clinical benefit rate (CBR), quality of life (QOL) and remission rate of clinical symptom. Results: From July 5 2007 to January 1 2008, 24 assessable entered in this trial screening in 45 NSCLC patients. Conclusions: No significant financial relationships to disclose.
Phase II, randomized study of GVAX pancreas and CRS-207 immunotherapy in patients with metastatic pancreatic cancer: Clinical update on long term survival and biomarker correlates to overall survival.
Authors: Chan Whiting, Eric Lutz, Nitya Nair, Serena Chang, Ed Lemmens, Shih- Yu Chen, Sara Solt, Sandy Ferber, Holden Maecker, Aimee Murphy, Dirk G. Brockstedt, Elizabeth M. Jaffee, Dung T. Le
Journal: Journal of Clinical Oncology (2015)

261 Background: In a phase 2a randomized study, metastatic pancreatic ductal adenocarcinoma (PDA) patients treated sequentially with two vaccine-based immunotherapies showed extended overall survival (OS) with tolerable side effects. Treatment included low-dose cyclophosphamide (CY) to inhibit T-regulatory cells prior to GVAX, an irradiated GM-CSF-secreting allogeneic PDA cell vaccine, which activates a broad antigenic response, followed by CRS-207, a live-attenuated, mesothelin-expressing Listeria monocytogenes vaccine which stimulates innate and adaptive immunity. Methods: Patients were enrolled with metastatic PDA who received or refused ≥1 prior chemotherapy, had ECOG ≤1 and adequate organ function. Patients were randomized 2:1 to receive 2 doses of CY/GVAX followed by 4 doses of CRS-207 (Arm A) or 6 doses of CY/GVAX (Arm B). PBMC and serum were collected over the course of treatment for immune and biomarker analyses. CyTOF, ELISPOT, and luminex were used to identify biomarker correlates of OS. Results: We previously reported phase 2a results demonstrating median OS in patients treated in arm A was 6.1 months compared to 3.9 months for those in arm B (HR=0.54, one-sided p=0.011). As of August 2014, 8 patients are still alive (median time on study: 768 days; range: 596-880), with 3 subjects on combination treatment. Mesothelin-specific CD8 + T cell responses following CY/GVAX correlated with improved OS in both arms. Elevated frequencies of T cell subsets and a panel of baseline serum cytokines also correlated with longer OS. Strikingly, hierarchical clustering based on expression of biomarkers showed significant clustering of patients according to OS. Conclusions: Treatment with CY/GVAX and CRS-207 was well-tolerated and resulted in improved OS compared to CY/GVAX alone. A larger phase 2b, 3-arm, randomized trial is ongoing and plans to treat 240 adults with previously-treated metastatic PDA with CY/GVAX and CRS-207, CRS-207 alone, or standard chemotherapy. Preliminary results using patients’ PBMCs and sera revealed potential biomarkers for OS. Clinical trial information: NCT01417000. Clinical trial information: NCT01417000.
Using the electronic medical record to identify and follow survivors of pediatric malignancies.
Authors: Elizabeth Bell, Robert Michael Cooper, Lisa Mueller
Journal: Journal of Clinical Oncology (2012)

302 Background: There are currently more than 328,000 survivors of pediatric malignancies in the United States (NCI, The Childhood Cancer Survivor Study: An Overview, http://www.cancer.gov/cancertopics/coping/ccss . 6/6/2012). These survivors are at risk for significant late effects from their cancer treatments (Childhood Cancer Survivors Study (Oeffinger, et al, NEJM 2006)). The Kaiser Permanente health care system has good insurance retention of patients treated for pediatric malignancies. Kaiser also uses an electronic medical record, which improves our ability to identify survivors and follow them over time to identify and manage late effects of cancer treatment. The Children’s Oncology Group (COG) has released a summary of cancer treatment form and specific guidelines for follow-up based on patients’ treatment. Methods: In 2010, we queried the Kaiser Permanente Southern California Cancer Registry for all patients who were diagnosed with a malignancy under the age of 18 from 1980 to 2009. This was cross-referenced with list of current Kaiser members as of 2010. We created a database of the current members and their diagnosis, treatment center, age at diagnosis, date of diagnosis, current age, years of survivorship, and sex. We divided the patients into priority groups: (1) more than 5 years from diagnosis and over age 18, (2) more than 5 years from diagnosis and less than age 18, and (3) less than 5 years from diagnosis. We began to prepare summaries of cancer treatment for the groups using the COG form. Results: We identified 1,267 survivors of pediatric malignancies who were Kaiser members in 2010. 54% are still Kaiser members 10 years after diagnosis. There were 611 in Group 1, 293 in Group 2, and 363 in Group 3. We have prepared summaries of cancer treatment including late effects for 400 of the survivors, 360 from Group 1, and 40 from Group 2. Conclusions: The combination of an electronic medical record and insurance retention allows us to identify and track survivors of pediatric malignancies into adulthood. With completed summaries of cancer treatment we will be able to quickly identify at-risk populations for monitoring and potential interventions.
Phase II trial of alternate schedule of chemotherapy as front-line treatment in metastatic non-small cell lung cancer (NSCLC): A single-centre experience
Authors: R. López Castro, G. Martín, R. Seijas, L. Bellido, E. del Barco, R. García, T. Martín, E. Castro, R. Leno, J. Cruz
Journal: Journal of Clinical Oncology (2008)

19120 Background: Tumor cell population is heterogeneus. It explains the variation in therapeutic response among patients with similar tumors, and the different tumor response intra-patient. This heterogeneity, due to mutations, selects cell sub-populations with natural or acquired resistance to therapeutic drugs. In order to overtake those known phenomena, in this phase II trial we propose the use of the four most active chemotherapeutic agents in NSCLC: Docetaxel, Gemcitabine, CDDP and Vinorelbine in an alternate schedule. Methods: Eligibility included stage IV or wet IIIB NSCLC. Additional criteria included an ECOG performance status of 0 to 2, absence of important comorbidities and the presence of at least one measurable lesion. Patients (pts) received an alternate schedule of treatment consisting of [Docetaxel 35 mg/m2 + Gemcitabine 800 mg/m2] d1 and 8; and [CDDP 35 mg/m2 + Vinorelbine 25 mg/m2] d21 and 29, every 6 weeks. 3 complete regimens would be administered. Primary end point was objective response per RECIST criteria. Secondary endpoints included progression-free survival (PFS) and safety. Results: 27 pts were enrolled. 3 of them left the protocol prematurely within 1st or 2nd infusion because of docetaxel hypersensitivity (1), severe hepatotoxicity (1) or life-threatening event (1). 21 were evaluable for response and 27 for safety (3 are now awaiting reevaluation with CT). 95.6% of the programmed treatments were administered. Median age was 58 years (range 41–75); 85% were male. Adenocarcinoma/squamous cell/undifferenciated non-small-cell carcinoma (48.1/18.5/33.3). Stage IIIB/IV (7.4/92.6); ECOG PS 0/1/2 (37/63/0). Clinical benefit was 81 % (CR 4.8%, PR 61.9%, SD 14.3% and PD 19%). PFS 9.7 months (3–20+). Toxicity: Anemia 55.5% (IV: 3.7%); Neutropenia 26% (III-IV: 11%); Mucositis 11% (III-IV: None); Nefrotoxicity 11% (III-IV: none); elevated AST and hyperbilirubinemia (III: 3.7%). Conclusions: Our results show that the combination of Docetaxel/Gemcitabine with Vinorelbine/Cisplatin in alternating schedule is a highly-active regimen in NSCLC stage wet IIIB/IV. Data of PFS, associated with the interesting toxicity profile, make it a feasible treatment to be taken into consideration in NSCLC. No significant financial relationships to disclose.
Effect of elevated expression of GST-π and p53 on prognosis in head and neck cancer patients treated with chemoradiotherapy but not radiotherapy alone: An analysis of RTOG trials 9003 and 9501
Authors: K. J. Cullen, N. Nikitakis, O. Goloubeva, M. Tan, R. Taylor, L. Schumaker
Journal: Journal of Clinical Oncology (2008)

6013 Background: Previously, a retrospective study showed elevated expression of glutathione s-transferase π (GST- π) and p53 is associated with poor outcome in a head and neck cancer patients treated with chemotherapy. Here we attempt to validate those findings in two cooperative group trials for locally advanced head and neck cancer. Patients with locally advanced disease were treated with radiation alone (RTOG trial 9003) or radiation ± concomitant chemotherapy as post operative adjuvant therapy (RTOG trial 9501). Methods: 393 of 1,113 patients from trial 9003 had tumor biopsies available. 142 of 459 patients from trial 9501 had tissue available. Immunohistochemical staining for p53 and GST-π was scored by a single pathologist. Results: Patients in both trials who had low expression of both markers had better survival than patients who were positive for both markers while patients with a single marker had an intermediate result. In the radiation only trial (9003) median survival was 2.4 years for patients negative for both markers versus 1.4 years for patients positive for both markers (p=0.07). In the radiation plus chemotherapy trial (9501), these differences were highly significant and were accounted for almost exclusively by the chemotherapy treated arm. In this group, patients negative for both markers had a median survival of 7.0 years compared to 1.4 years for patients positive for both markers (p=0.006). For the radiation only arm, the markers were not predictive of survival (p=0.54). In both trials, black patients had lower survival rates than did white patients and there was a trend toward higher expression of both markers in blacks compared to whites. Conclusions: Given the poor outcome of chemoradiotherapy treatment patients with elevated expression of both p53 and GST-π, these patients may not be ideal candidates for chemoradiotherapy based on standard protocols. Conversely, patients with low expression of both markers appear to be good candidates for combined chemoradiotherapy and will have a favorable outcome. Some of the adverse outcomes for black patients in both studies may be attributed to elevated expression of p53 and GST-π. No significant financial relationships to disclose.
Phase II study of bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater.
Authors: Pat Gulhati, Kanwal Pratap Singh Raghav, Rachna T. Shroff, Gauri R. Varadhachary, Scott Kopetz, Milind M. Javle, Wei Qiao, Huamin Wang, Jeffrey Morris, Robert A. Wolff, Michael J. Overman
Journal: Journal of Clinical Oncology (2016)

144 Background: Capecitabine with oxaliplatin (CAPOX) is used in front-line management of metastatic small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). In a prior single arm phase 2 study (n = 30), CAPOX showed an overall response rate (ORR) of 52%. The purpose of this study was to evaluate safety and activity of bevacizumab and CAPOX in this population. Methods: We conducted a single-center open-label single arm phase 2 study in patients with treatment naïve metastatic SBA and AAC between 8/2011 to 11/2014. Prior fluoropyrimidine-based adjuvant therapy was allowed if completed ≥ 52 weeks. Bevacizumab-CAPOX was administered as a 21-day cycle with capecitabine 750 mg/m 2 orally twice daily on days 1-14, oxaliplatin 130mg/m 2 intravenously on day 1 and bevacizumab 7.5mg/kg intravenously on day 1. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary objectives included ORR, overall PFS, overall survival (OS) and toxicity. Results: A total of 30 patients with median age of 63 years (range 33-78) were enrolled. Six (20%) patients had AAC and 24 (80%) had SBA (duodenal: 18). Treatment was well tolerated and most common grade 3/4 toxicities included fatigue (23%), hypertension (23%), neutropenia (30%), and diarrhea (10%). Common grade 2 toxicities included anorexia (50%), fatigue (47%), and nausea (37%). 4 patients remain on study treatment to date. In 29 evaluable patients the ORR was 48.3% (1 complete and 13 partial responses). Eleven (37.9%) patients had stable disease. The PFS at 6 months was 68% (95% CI: 52%-88%). The median PFS and median OS were 8.7 (95% CI: 6.6-13.4) and 14.98 (95% CI: 10.2-21.3) months, respectively. Comparing the current study to a subset of 25 patients with metastatic disease from our prior phase 2 CAPOX study demonstrated similar ORR, 48.3% vs. 52% (p = 0.79) and PFS 8.7m vs. 6.6m (p = 0.73). Conclusions: In patients with untreated metastatic SBA and AAC, therapy with bevacizumab and CAPOX was well-tolerated and showed efficacy comparable to published regimens. Further studies are warranted to evaluate the benefit of targeting angiogenesis in this rare tumor.
Therapeutic effect and basic research on high-dose toremifene to reduce anticancer drug resistance in breast cancer
Authors: M. Kusama, H. Kaise, D. Ota, T. Aoki, S. Kuroiwa
Journal: Journal of Clinical Oncology (2005)

846 Background: It has been reported that the antiestrogen agent (SERM) has a resistance relief function when it bind to P-glycoprotein (Pgp) and supresses pumping action. A blood concentration of the antiestrogen agent at 2.5 to 10μM is required in order to have the in vitro manifestation of the effect. Our studies demonstrated that the toremifene citrate (TOR), which has the function, at 120mg, the oridinary dose used in Japan, produced the combined blood concentration of TOR and its metabolite N-desmethyltoremifene (TOR-1) at 5 to 10μM. This study presents basic data and clinical effects of TOR coadministrered to cases resistant to anthracycline. Methods: In 13 recurrent breast cancer patients with 2 or less regimens of prior chemotherapy (including adjuvant chemotherapy), 3 cycles of CAF therapy alone was performed as initial or secondary therapy, and patients for whom the therapy was ineffective (NC or PD) received concomitant administration of high-dose TOR. Biopsy of the recurrent lesion was possible in 5 patients, and the expression of Pgp was detected by immunohistological staining. Results: One cycle of therapy consisted of 28 days of ADM (25 mg/m2) and 5-FU (500 mg/m2) administered on days 1 and 8, and cyclophosphamide (CPA) and high-dose TOR were orally administered daily from day 1 to 14. Finally, 3 of the 13 patients (23.1%) responded to the treatment, and 1 patient was CR. Clinical benefit was obtained in 6 patients (46.1%). The median duration of effect including clinical benefit was 351 days, and average survival was 493 days. The median of the duration of the effect in the responder patients was 355 days, and the average number of survival days was 582 days. No potentiation of adverse effects requiring treatment was observed. Pgp was detected in all 5 patients who underwent biopsy, and the effect was PR in 2 and NC in 2 patients. Conclusions: Concomitant administration of high-dose TOR to patients with multiple drug-resistant recurrent breast cancer may increase the effective rate and duration of the effect by overcoming resistance. No significant financial relationships to disclose.
Pattern of recurrence after curative surgery in thoracic esophageal squamous cell carcinoma: A 6-year experience with 1,020 patients.
Authors: W. Mao, Y. Xu, J. Liu, S. Ma, X. Zhou, Q. Chen, X. Zheng, X. Du
Journal: Journal of Clinical Oncology (2011)

e14557 Background: The knowledge of patterns of recurrence for patients with esophageal carcinoma will be of great value in a clinic when designing therapeutic strategies. The current study reports mode, timing and predictive factors of recurrence after curative surgery for thoracic esophageal squamous cell carcinoma (TESCC). Methods: A retrospective study in a series of 1,020 curatively (R0) resected patients from 2003 to 2008 at Zhejiang Cancer Hospital. Results: The 2 and 5 years recurrence rate were 39.0% and 59.2% respectively. Variables associated with a higher rate of recurrence on univariate analysis were male, length of tumor ≥5cm, deeper depth of invasion, more lymph node metastasis, higher histologic grade, vessel involvement positive, postoperative radiotherapy and postoperative chemotherapy. By multivariate analyses, gender (HR 1.7; 95%CI 1.2–2.5; p=0.002), depth of invasion (HR 1.4; 95%CI 1.2–1.6; p<0.001), lymph node involvement (HR 1.4; 95%CI 1.3–1.5; p<0.001) and postoperative adjuvant radiotherapy (HR 1.3; 95%CI 1.0–1.6; p=0.026) or chemotherapy (HR 1.5; 95%CI 1.2–1.8; p=0.001) were independent predictive factors of recurrence. Less than 10% patients with more than 10 metastatic nodes were free from relapse 3 years after surgery. More than 85% recurrence occurred within 36 months. Postoperative radiotherapy or chemotherapy didn't prolong failure free survival (FFS) significantely, especially in patients with early-stage disease. Conclusions: Gender, depth of invasion, lymph node involvement and postoperative adjuvant therapy were independent predictors of recurrence. Postoperative radiotherapy or chemotherapy didn't prolong FFS significantely. For patients with R0 resection of TESCC, postoperative adjuvant radiochemotherapy need to select appropriate patients.