tbuckley/cabot-search huggingface dataset:
Screening for self-efficacy and distress: A report from the “Resilience in Adolescents and Young Adults with Cancer” study.
Authors: Abby R. Rosenberg, Miranda Bradford, Kira O'Neil Bona, Michele Shaffer, Joanne Wolfe, Karen Syrjala, Kevin Scott Baker
Journal: Journal of Clinical Oncology (2015)

e21037 Background: Adolescents and Young Adults (AYAs) with cancer and their parents are at risk for poor psychosocial outcomes. We aimed to determine if early patient-reported psychological distress, resilience, and self-efficacy were predictive of later distress. Methods: The “Resilience in Adolescents and Young Adults with Cancer” study was a prospective, multi-center, mixed-methods cohort study. English-speaking 14-22 year-old patients with newly diagnosed cancer and their parent(s) were invited to complete a comprehensive survey at the time of enrollment (T1) and 3-6 months later (T2). Psychological distress was assessed with the Kessler-6 scale, resilience with the Connor-Davidson Resilience scale, and self-efficacy with the Snyder Hope scale, including agency and pathway subscales. We first plotted T1 instrument scores vs. T2 distress, and then used multivariable linear regression to estimate the strength of associations. Results: To date, 21 patients (mean age 18 years [SD = 2], 57% female) and 27 parents (mean age 44 years [SD = 15], 67% mothers) have completed surveys at both time-points. Moderate-high distress was reported at T1 and T2 by 37% and 19% of AYAs, and 43% and 41% of parents, respectively. Lower resilience, lower self-efficacy and higher distress at T1 were associated with higher distress at T2 for both patients and parents. Resilience failed to reach significance in a multivariable model including all T1 scores and adjusting for age and gender, but T2 distress decreased by 0.3 points (95% CI -0.1, -0.5) for every one-point increase in T1 Hope-pathway score and increased by 0.4 point (95% CI 0.1, 0.6) for every one-point increase in T1 distress. Conclusions: AYA patient- and parent-reported self-efficacy and distress at the time of diagnosis are predictive of later distress. Comprehensive assessments near the time of diagnosis may identify those in need to additional support during or after treatment.
A phase II trial of image-guided radiofrequency ablation of small breast carcinomas: Results of a multicenter study in Japan
Authors: T. Kinoshita, N. Yamamoto, T. Fujisawa, N. Masuda, T. Hojo, K. Aogi, K. Seki, H. Tsuda
Journal: Journal of Clinical Oncology (2009)

e11535 Background: Locally ablative therapy of early breast cancer represents the next frontier in the evolution of minimally invasive breast conservative therapy. We performed this Phase II trial to determine the efficacy and safety of Radiofrequency (RF) ablation of small localized invasive breast carcinomas as a multicenter study in Japan. Methods: Thirty-nine patients with core-biopsy proven invasive breast cancer, T&lt;2 cm in diameter on ultrasound and MRI were enrolled in this trial. Under ultrasound guidance, the tumor and at least a 5mm margin of surrounding breast tissue were ablated with saline- cooled RF electrode followed by surgical resection. Pathologic and immunohistochemical stains were preformed to assess tumor viability. Results: Thirty-seven patients completed the treatment. The mean tumor size on ultrasound was 1.50 cm. The mean ablation time was 12 minutes using mean power of 80.0 watts. During ablation, the tumor became progressively echogenic that correspond with the region of sever electrocautery injury at pathologic examination. Of the 37 treated patients, H&amp;E and NADPH viability staining was available for 27 patients and in 25 (92.5%), there was no evidence of viable cancer cells. H&amp;E and or ssDNA staining were available for another 10 patients. In total, complete thermal injury to the target lesions was recognized in 33 of 37 treated patients (89.2%). No sever adverse effect on the skin and chest wall were noted. Conclusions: RF ablation is a promising minimally invasive treatment of small breast carcinomas, as it can achieve effective cell killing with a low complication rate. We are planning a multicenter observation study for RF ablation of small breast carcinomas. No significant financial relationships to disclose.
Abnormalities of the Bone Marrow Immune Microenvironment in Patients with Prolonged Isolated Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Yang Song, Yuan Kong, Min-Min Shi, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
Journal: Blood (2016)
Multicenter institutional experience of surgically resected thymic epithelial tumors (TETs): An observational report.
Authors: Giovenzio Genestreti, Marco Angelo Burgio, Luca Ampollini, Luigi Rolli, Stefano Sanna, Emanuela Scarpi, Salvatore Luca Burgio, Dino Amadori
Journal: Journal of Clinical Oncology (2012)

e17546 Background: Thymic epithelial tumors (TETs) consist of a series of neoplasm arising from the anterior mediastinum. Due to its rarity, large-scale prospective trials have been lacking. This retrospective multicenter analysis aimed to evaluate clinical outcome and clinico-pathological features of TETs after surgery resection and adjuvant treatments as chemotherapy and/or radiotherapy. Methods: All medical records about TETs surgically resected between 2000 and 2007 and eventually treated with adjuvant therapies (chemotherapy and/or radiotherapy) were reported. Surgical procedures included complete removal of thymic, mediastinal fat tissue and any suspicious lesions. Histological classification has been made in according to WHO criteria and Masaoka staging system was adopted. Adjuvant chemotherapy was represented by anthracycline and platin-based regimen whereas adjuvant radiotherapy was delivered on irradiation field covered primary tumor bed. Overall survival was calculated from the date of diagnosis until patient death or last follow-up visit. Disease free-survival was defined the interval from operation until date of recurrence. Results: Overall 32 patients were analyzed of whom 12 (37%) male and 20 (63%) female. Median age was 61 years (range: 33 - 86). At the beginning of their oncologic history 14 (42%) patients had miastenia. Overall at clinical staging there were 19 (60%) stage I, 4 (12%) stage II, 4 (12%) stage III, and 5 (16%) stage IVb at radiological staging. The histological exam reported: 5 (16%) A tumor type, 11 (34%) AB type, 3 (10%) B1 type, 3 (10%) B2 type, 8 (24%) B3 type, 2 (6%) C type. At pathological staging there were: 18 (56%) stage I, 7 (22%) stage II, 2 (6%) stage III and 5 (16%) stage IVb. Post-surgical therapies were represented by chemotherapy in 2 (6%) patients and radiotherapy in 13 (41%) patients. Disease relapse was recorded in 1 (3%) patient after 27 months from diagnosis. Overall survival rate at 78 months is 86% (CI: 66-100). Conclusions: TETs are rare and indolent cancer. Surgery offers the good perspectives eventually improved with adjuvant therapies like chemotherapy and/or radiotherapy. Supported by GIPO.
Predictive serum biomarkers in metastatic colorectal cancer (mCRC) patients treated in the BECOX trial with oxaliplatin-capecitabine (CAPOX) plus bevacizumab (BVZ) (GEMCAD 09-01).
Authors: Estela Pineda, Antonieta Salud, Elena Vila-Navarro, Maria Jose Safont, Carlos Garcia-Giron, Jorge Aparicio, Ruth Vera, M. Pilar Escudero, Enrique Casado, Carlos Bosch, Uriel Bohn, Ramon Maria Perez Carrion, Alberto Carmona Bayonas, Juan Ramón Ayuso, Tomas Ripolles, Rosa Bouzas, Meritxell Gironella, Xabier Garcia-Albeniz, Jaime Feliu, Juan Maurel
Journal: Journal of Clinical Oncology (2015)

e14647 Background: Despite initial responsiveness, acquired resistance to both BVZ and chemotherapy in mCRC is universal. We have recently published that, chronically oxaliplatin resistant LoVo cell line (LoVo-R) up-regulates soluble VEGF receptor 1 (sVEGFR1), down-regulates vascular endothelial growth factor (VEGF) and also promotes c-MET compared with the parental LoVo cell line (Mezquita, Mol Carcinogenesis 2015). We tested whether variation in three serum biomarkers, VEGF, sVEGFR1 and the hepatocyte growth factor (HGF), were associated with efficacy in mCRC patients (pts) treated in the prospective BECOX study. Methods: Serum levels of VEGF, sVEGFR1 and HGF (the c-MET ligand) were assessed by ELISA method assay basally, and every 3 cycles in a pre-planned translational study. Response was evaluated using RECIST 1.1 criteria by Investigators assessment (IA) and by three blinded independent radiologists (IR), and using morphologic criteria (Chun, JAMA 2009) by IR. Ratios variations of sVEGFR1/VEGF and HGF/VEGF through time were related to RECIST 1.1 and morphologic responses. Results: The BECOX trial included 68 pts and 27 pts were analyzed in the translational trial. A total of 80 RECIST 1.1 evaluations were done by IA and 56 by IR. We found that responders had a 3.22 and 3.06 (by IA and IR respectively) sVEGFR1/VEGF fold increase from previous determination compared with a 1.38 (IA) and 1.59 (IR) fold increase in non-responders (p = 0.0009 and p = 0.03 respectively). Moreover, responders had a 3.36 (IA) and 3.66 (IR) HGF/VEGF fold increase compared with a 1.43 (IA) and 1.53 (IR) fold increase for non-responders (p = 0.002 and 0.003 respectively). No association between serum biomarkers and efficacy was observed in 49 evaluated pts using morphologic response criteria. Conclusions: A decrease on VEGF and an increase of sVEGFR1 during chemotherapy and BVZ exposure, can contribute to both chemotherapy (due to c-MET activation) and BVZ resistance. Because HGF levels decrease also during acquired resistance, alternative strategies to HGF-c-MET inhibition should be investigated. Clinical trial information: GEMCAD 09-01.
Stage III NSCLC: How many patients are really suitable for radical treatment approaches?
Authors: Humaid Obaid Al-Shamsi, Peter Michael Ellis
Journal: Journal of Clinical Oncology (2012)

e17532 Background: Stage III NSCLC represents a heterogeneous population. Patients with good performance status (PS) and weight loss &lt; 10% (WL&lt;10) are generally considered for radical treatment with chemoradiation or trimodality approaches. Outcome data from Cancer Care Ontario show 30% of stage III NSCLC (6th edition TNM) patients receive chemoradiation.There is significant variation between local health networks. We examined the proportion of patients with stage III NSCLC suitable for radical treatment. Methods: We conducted a retrospective cohort study of patients diagnosed with stage III NSCLC at the Juravinski Cancer Center from July 2007 to June 2009. Demographic, pathologic and treatment data were abstracted from patients’ records. The primary outcome was the proportion of stage III NSCLC patients eligible for radical treatment. We also compared patients treated radically versus palliatively. Results: 159 stage III NSCLC patients (staged by 6th edition TNM) were seen. The median age was 69 yrs (sd 12) with 58% men and 42% women. There were 40% stage IIIA, 37% IIIB and 23% IIIB (wet). 61 (38%) patients were treated with radical intent and 98 (62%) were treated palliatively. Reasons for palliative treatment approach were WL &gt;10% (7%), PS &gt;2 (10% ), both WL &gt;10% and PS &gt;2 (20%), significant comorbidities (9%),patient declined (9%) and stage IIIB wet(23 %).The median OS for patients treated radically was 23.3 months v 7.1 months for those treated palliatively. Stage IIIA patients treated radically had better OS than IIIB (27m v 14m). Patients with poor PS, or WL&gt;10% had similar OS to patients with wet stage IIIB (7.1m v 7.2m), whereas the survival of patients with poor PS and WL &gt;10% was worse (3m). Conclusions: Using eligibility criteria from clinical trials of stage III NSCLC, only 40% of patients appear eligible for radical treatment approaches. Our data are consistent with published data. Significant WL&gt;10% or poor PS (&gt;2) predicted poor outcome. Combined WL&gt;10% and poor PS predicted a very poor prognostic group. Criteria for radical treatment of stage III NSCLC should not be extrapolated beyond the eligibility criteria used in clinical trials.
Genetic and cytokine profiles associated with symptomatic stage of CLL.
Authors: Amit Balkrishna Agarwal, Laurence Cooke, Christopher Riley, David Mount, Daruka Mahadevan
Journal: Journal of Clinical Oncology (2013)

7062 Background: Pathogenesis of symptomatic CLL involves genetic changes associated with the CLL clone and changes within the microenvironment which contribute to chemo-resistance. To further understand these processes we compared early stage CLL to symptomatic late stage CLL using gene expression profiling as well as serum cytokine profiling for a better insight of the genetic and microenvironment changes associated with the most severe forms of the disease. Methods: We obtained pretreatment blood samples from CLL patients (10 low stage and 14 high stage) at the time of diagnosis. Patients were classified as low stage (Rai stage 0/I/II) and high stage (Rai stage III/IV). Gene expression profiles were obtained on a subset of patients using the HG-U133A 2.0 Affymetrix platform and analyzed for differential gene expression profiles. Serum from a subset of patients was used to perform cytokine profiling using the Raybiotech Cytokine Array platform (AAH-CYT-G1000) that allows for simultaneous measurement of &gt;100 different cytokines. Results: Comparison of low versus high stage CLL revealed a set of 21 differentially expressed genes. 15 genes were up regulated in the high stage versus low stage, while 6 genes were down regulated. GO Molecular function analysis revealed that 9 of the 21 genes are involved in transcription factor activity. Other genes up regulated in the high stage group include CSNK1- shown to be involved in Myc derived oncogenesis and SETD8- a histone lysine methyltransferase previously implicated in several cancers. Serum cytokine profiles showed 6 cytokines to be significantly different in high stage patients. Two chemokines SDF-1/CXCL12 and uPAR known to be involved in stem cell mobilization and homing are increased in the serum of high stage patients. IGFBP-2, BMP-4 and MCP-4 were lower among high stage patients. Conclusions: Our study revealed a novel group of transcription factors are associated with higher stage CLL. Cytokine profiling showed increased levels of SDF-1/CXCL12, a chemokine that plays a key role in mobilization and homing of hematopoietic stem and CLL cells in high stage patients. Our study identifies putative therapeutic targets including CSNK1, SDF-1 and SETD8 for patients with high stage CLL.
Phase II trial of pemetrexed disodium and gemcitabine in advanced carcinoma of the urothelium (E4802): A trial of the Eastern Cooperative Oncology Group
Authors: S. Li, R. Dreicer, B. Roth, J. Manoloa, M. Cooney, G. Wilding
Journal: Journal of Clinical Oncology (2007)

5079 Background: Advanced urothelial carcinoma is a moderately chemosensitive disease. Although the gemcitabine/cisplatin regimen has essentially replaced M-VAC as front-line therapy, both regimens are moderately toxic and produce similar response rates and median survival. Pemetrexed is a novel multi-targeted antifolate with single agent activity in advanced urothelial cancer. We evaluated pemetrexed in combination with gemcitabine in untreated pts with advanced urothelial cancer. Methods: Patients with TCC or mixed histologies received pemetrexed 500 mg/m 2 IV over 10 minutes followed by gemcitabine 1,000 mg/ m 2 IV over 30 minutes on day 1, with gemcitabine repeated on day 8 of a 21-day cycle. Dose reductions were mandated for grade 3/4 toxicities. Patients remained on treatment until disease progression or unacceptable toxicity or a maximum of 6 cycles of therapy. Standard RECIST criteria were used to assess response. Results: Total accrual was 46 pts. Two pts never started therapy and were excluded, leaving 44 pts included in the analysis. The pt cohort was 36 (82%) male and 42 (95%) Caucasian. Twenty-two pts (50%), 21 (48%) and 1 (2%) had 0, 1 and 2 MSKCC risk factors respectively. Seventy-five percent of pts had distant metastatic disease at study entry including 7 (16%) with liver, 3 (7%) bone and 14 (32%) lung metastases. A median of 4 cycles were administered (range, 1–6). The most common reasons for discontinuing treatment were progressive disease (27%) and toxicity (20%). Eighteen pts experienced grade 4 toxicities, including leukocytes (n=5), neutrophils (n=18), cardiac arrest, fatigue, infection with grade 3 or 4 neutropenia (n=1 pt each). Two pts died from grade 5 toxicities while receiving treatment: one death was from neutropenia and the other pt died from infection without neutropenia following sepsis and subsequent cardiac arrest. Response information is available for 39 pts. There has been 1 complete response and 10 partial responses with an overall response rate of 28% (90% CI: [17%, 42%]). Eleven pts had stable disease for at least 6 weeks. Conclusions: Pemetrexed/gemcitabine has modest activity in patients with previously untreated advanced TCC of the urothelium, but at the cost of significant toxicity. [Table: see text]
Detection of satellite alpha transcript in sera, as a surrogate marker for the risk of development of multiple cancers in colorectal cancer patients.
Authors: Kosuke Ichida, Koichi Suzuki, Yuji Takayama, Yuta Muto, Taro Fukui, Takaharu Kato, Masaaki Saito, Fumiaki Watanabe, Nao Kakizawa, Hirofumi Imoto, Hiroyuki Tanaka, Yuji Kaneda, Yusuke Taniyama, Shingo Tsujinaka, Osamu Takata, Yasuyuki Miyakura, Hiroshi Noda, Hirokazu Kiyozaki, Fumio Konishi, Toshiki Rikiyama
Journal: Journal of Clinical Oncology (2015)

e22044 Background: Non-cording RNA, satellite alpha transcript (SAT-a) plays an important role on mitosis, disruption of which leads to genomic damages. We have reported that increased levels of SAT-a were observed not only in cancer tissues, but also in non-cancerous tissues, which was involved in the mechanisms underlying the development of multiple cancers. In this study, we determined the levels of SAT-a in sera comparing between colorectal cancer (CRC) patients with or without multiple cancers. Methods: Plasma samples were collected from 95 CRC patients including 36 patients with a single tumor (S) and 59 patients with multiple cancers (M). Twenty-one patients had multiple colorectal tumors (M-c) and 38 patients harbored extra-colonic primary tumors (M-ex). The levels of SAT-a were compared between S and M by real-time PCR. Results: The levels of SAT-a did not correlate with age or stage. No difference in stage may indicate that SAT-a is not supplied from cancerous tissues. The most frequent organ to develop extra-colonic tumors was stomach (60.5%). Comparing S and M, no difference in age was seen but M significantly favored male over female, which could be due to stomach cancers to be likely developed in male. The levels of SAT-a was significantly increased in M (264.0±60.7) as compared with S (95.9±15.4). Comparing patients in M, the levels of SAT-a in M-c (313.4±136.1) is likely higher than M-ex (236.6±58.2) , but no significant difference was seen. Then we focused on the sites of extra colon, revealing that the levels of SAT-a in gastrointestinal organs (stomach and esophagus; 321.2±91.9) is likely higher than others (lung and others; 102.6±17.5, p = 0.056). Conclusions: The levels of SAT-a in sera could be a surrogate marker for the risk of development of another gastrointestinal cancers in CRC patients.  Single (S); n = 36 Multiple(M); n = 59 P value S vs. M M-colon (M-c); n = 21 Extracolon (M-ex); n = 38 Age  66.8±1.5 69.9±1.1 NS 69.0±2.1 70.0±1.2 Gender Male 18 44 0.015 17 27 Female 18 15 4 11 Stage I-III 20 42 NS 10 32 IV 16 17 11 6 Sites of mutiple tumors colon 0 23  21 2 stomach 0 23 0 23 lung 0 12 0 12 esophagus 0 3 0 3 others 0 3 0 3  SAT-a 95.9±15.4 264.0±60.7 0.029  313.4±136.1 236.6±58.2
Association of bone scan index (BSI) with prognostic biomarkers and survival in men with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a prospective randomized controlled trial of tasquinimod.
Authors: Andrew J. Armstrong, Reza Kaboteh, Michael Anthony Carducci, Jan-Erik Damber, Walter Michael Stadler, Hansen Mats, Lars Edenbrandt, Goran Forsberg, Orjan Nordle, Roberto Pili, Michael J. Morris
Journal: Journal of Clinical Oncology (2013)

5081 Background: Tasquinimod (T) is an oral immunomodulatory and anti-angiogenic agent currently in phase 3 testing in mCRPC. In a randomized, double-blind phase 2 multicenter study, 201 men with mCRPC who received T had improved radiographic PFS vs. placebo (P), with a more pronounced effect seen in men with bone metastases. Given the subjectivity/variability of bone scan measurements, we sought to evaluate the bone scan index (BSI), a quantitative and objective measure of BS activity, over time in this controlled clinical trial. Post-treatment BSI changes were examined given their prior association with survival. Methods: In this retrospective analysis, Exini bone™, an automated software package that generates the BSI (percent tumor involvement) from 99 Tc BS, was used to calculate BSI over time from BS collected during central review in this randomized trial of T vs. P. Associations between baseline and on-treatment BSI, survival, prognostic biomarkers, and treatment effect were evaluated. Results: 108 men contributed baseline scans for BSI analysis that met quality control metrics (74 T vs. 34 P), 85 of whom (57 T vs. 28 P) had at least 1 evaluable follow-up week 12 scan. Median baseline BSI was 0.90% and after 3 months median BSI was 1.21%. In univariate analysis (n=85) baseline BSI correlated with OS (HR 1.41; p=0.01). Both baseline BSI (HR 1.62; p=0.006) and week 12 BSI change (HR 1.95; p=0.002) remained associated with OS after adjustment for bone alkaline phosphatase, PSA, pain score, hemoglobin, and treatment arm. BSI correlated with baseline PSA, LDH, bone alkaline phosphatase, and the number of bone lesions. The increase in BSI at week 12 vs. baseline was slower with T vs. placebo (0.16% vs. 0.26% increase). Conclusions: BSI and BSI changes were associated with OS in men with mCRPC in this prospective trial. BSI correlates with known biomarkers of OS, but adds independent prognostic information. While underpowered, a delay in objective radiographic bone scan progression with tasquinimod is suggested and the evaluation of BSI and BSI changes in the context of phase 3 trials of men with mCRPC is warranted. Clinical trial information: NCT00560482.