tbuckley/cabot-search huggingface dataset:
Results of a randomized prospective clinical trial evaluating maintenance chemotherapy in patients with high-grade, operable osteosarcoma: A report from the Latin American Group of Osteosarcoma Treatment.
Authors: Antonio Sergio Petrilli, Carla R. Macedo, Sima Ferman, Marcelo Scopinaro, Walter Cacciavillano, Erica Boldrini, Vera Lucia L. Morais, Guadalupe Leticia Rey, Claudia T. de Oliveira, Luis Alberto Castillo, Maria Teresa A Almeida, Maria Luisa Borsato, Eduardo Lima, Daniel Lustosa, Jose Henrique Barreto, Algemir Lunardi Brunetto, Tatiana EL-JAICK B. Costa, Simone Dos Santos Aguiar, Marcelo Petrilli, Maria Teresa de Seixas Alves
Journal: Journal of Clinical Oncology (2014)

10532 Background: Preclinical models show that a daily antiangiogenic regimen at low-dose may be effective against chemotherapy-resistant tumors. In patients (pts) with high grade, operable osteosarcoma (OST) of the extremities, efficacy of maintenance therapy with continuous oral cyclophosphamide and methotrexate was investigated. Methods: Pts ≤30yrs with high-grade OST were eligible for registration at diagnosis. Eligibility for randomization included: 1. Non-metastatic pts 2. high-grade extremity OST 3. receipt of two cycles pre-operative methotrexate, doxorubicin, cisplatin (MAP); 4. complete macroscopic resection of primary tumor. The study design includes a backbone of 10 weeks of preoperative therapy using MAP. Following surgery, non-metastatic pts were randomized by blocks to complete 31 weeks of MAP or to receive 73 weeks of maintenance therapy following MAP; while metastatic pts received maintenance therapy in combination with MAP since the beginning of treatment. The primary end point was event-free survival (EFS) from randomization. Results: Of the 682 pts registered (April, 06 to July, 13) from 3 countries (27 sites), 535 were evaluable, mean age at enrollment of 13.5 years, mean time to diagnosis of 3.8 months and metastatic disease in 38% of the pts. The multivariate analysis showed that metastases at diagnosis (p<0.001), necrosis grades 1 and 2 (p=0.001) and amputation (p=0.02) were associated with a shorter EFS. In the whole cohort of pts, overall survival (OS) was 62% at 5 years and event free survival (EFS) was 50%. For non-metastatic pts, OS was 72% and EFS was 60%. There was no significant difference in EFSbetween pts who received MAP+maintenance chemotherapy comparedwith MAP alone (61% vs 64%, log-rank test p=0.3). Conclusions: OST survival rates were improved by the use of this regimen compared with previously reported results by the group. However, with current follow-up, EFS for MAP+maintenance chemotherapy is not statistically superior to MAP alone in pts with high-grade resectable OST of the extremities. Further follow-up for events and survival continues.
Synovial sarcoma: Is chemotaxis important to tumor progression?
Authors: Emanuela Palmerini, Maria Serena Benassi, Stefania Benini, Laura Pazzaglia, Eric L. Staals, Gabriella Gamberi, Marco Gambarotti, Piero Picci, Stefano Ferrari
Journal: Journal of Clinical Oncology (2013)

10571 Background: Synovial sarcoma (SS) is a rare and aggressive soft tissue tumor. In a first study (Palmerini E, Cancer 2009) we analyzed clinical prognostic factors in a retrospective series of 250 patients (pts) who were treated at Rizzoli Institute between 1976 and 2006. Stage, age, size, histology and use of radiotherapy influenced survival, whereas the role of chemotherapy was unproven. In the present study on the same patient population, in order to identify new prognostic factors and potential therapeutic targets, a panel of markers involved in chemotaxis and tumor growth were assessed. Methods: The expression of the chemokine receptor CXCR4 (a marker for chemotaxis which plays a critical roles in cancer progression) and the insulin-like growth factor receptor-1 (IGFR1) (a marker of growth activation ) were evaluated by IHC staining. Results: Tissue samples were available for the analysis in 88 patients (45 female and 43 male); median age was 37 years (range 11-63); size of the lesion was &gt; 5 cm in 60 patients (71%); histology was biphasic in 30 (34%) of patients. All pts underwent surgery, 56% of pts underwent adjuvant radiotherapy (RT) and 68% adjuvant chemotherapy. With a median follow-up of 6 years (1-30 years), the 5-year overall survival (OS) was 70% (60-81). A positive stain for IGFR1 was detected in 55 pts (62.5%), with expression in the nucleus in 21 pts. CXCR4 was expressed in 74 pts (84%), nuclear pattern in 31 pts. No relation between IGFR1 and CXCR4 expression and clinical variables was found. The 5-year OS was 63% (95%CI 41-85%) for pts with positive IGFR1/nuclear expression and 73% (95%CI 61-85%) p = 0.05, in pts with negative IGFR1/nuclear staining. Similarly, the 5-year OS was 47% (95%CI 27-66%) in patients with positive CXCR4/nuclear expression and 86% (95%CI 76-96%), p = 0.003, in negative cases. In a multivariate analysis including age, histology, size and use of RT, nuclear expression of IGFR1 and CXCR4 were confirmed statistically significant independent factor for OS. Conclusions: The nuclear expression of CXCR4 or IGFR1 negatively influences the survival in patients with SS. Further studies addressing the role of CXCR4 as a potential target in this high risk subgroup of SS patients are needed.
Clinical experience with exemestane in postmenopausal women at increased risk of breast cancer.
Authors: Mia Sorkin, Donna Lapolt, Lajos Pusztai, Erin Wysong Hofstatter
Journal: Journal of Clinical Oncology (2013)

1565 Background: Exemestane has recently been identified as an effective breast cancer chemoprevention agent. This drug may be more appealing to patients than tamoxifen or raloxifene, since it does not increase the risks of thrombosis, cataracts and uterine cancer. Poor patient acceptance of tamoxifen and raloxifene as chemoprevention is well-documented but patient acceptance rates for exemestane have not been reported. The goal of this study was to assess exemestane use in a breast cancer prevention clinic. Methods: A retrospective chart review was conducted to capture patient characteristics, medical history and chemoprevention uptake of all postmenopausal women presenting to the Yale Breast Cancer Prevention Clinic from November 2011-November 2012. Descriptive statistics are presented. Results: Fifty-six postmenopausal women deemed eligible for initiation of chemoprevention were seen during the study timeframe, with a mean age of 58 (range 42-79). Risk categories included: 22 women (39%) diagnosed with breast atypia, 7 with LCIS (12%), 4 with prior DCIS (7%), 41 with family history of breast cancer (73%), and 8 women with a deleterious BRCA 1 or 2 mutation (14%). 22 (39%) of these women had osteopenia or osteoporosis. Of all eligible women, 13 opted to start a chemoprevention medication (23%); 8 of whom opted for raloxifene, 1 for tamoxifen and 4 for exemestane. While exemestane comprised 30.7% (4/13) of chemoprevention medication uptake, only 4 of 56 women eligible for chemoprevention decided to take exemestane (7%). Conclusions: Chemoprevention uptake rates of postmenopausal women in the setting of a breast cancer prevention clinic are higher (23%) than those reported in the general population, but remain low overall. Uptake of exemestane appears lower than that of raloxifene but higher than tamoxifen. A large proportion of postmenopausal women (39%) have osteopenia or osteoporosis which limits exemestane uptake in a breast cancer prevention setting.
Comparison of multiparametric MRI to PSA kinetics as an indication of prostate cancer progression in men on active surveillance.
Authors: Mahir Maruf, Michael Kongnyuy, Arvin Koruthu George, Mohummad Minhaj Siddiqui, Abhinav Sidana, Amit L Jain, Brian P. Calio, Dordaneh Sugano, Raju Chelluri, Subin Valayil, Akhil Muthigi, Thomas P Frye, Peter L. Choyke, Baris Turkbey, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2017)

59 Background: Pathologic progression is identified in &gt; 25% of prostate cancer (CaP) patients on active surveillance (AS). Yet, identifying patients at risk for progression is limited to PSA based biomarkers with variable utility. Multiparametric MRI (mpMRI) with fusion-guided prostate biopsy (FBx) has shown utility in risk stratification for patients considering AS. We compared mpMRI characteristics with PSA kinetics for the prediction of pathologic progression in AS patients. Methods: A review of men on AS with serial mpMRI and 2 or more FBx sessions was performed. FBx sessions consisted of targeted biopsies and a 12 core systematic biopsy. Men who met NIH Expanded AS criteria included those with low and intermediate risk CaP, Gleason score ≤ 3+4 = 7 with no restriction on percent core involvement or number of cores positive. Progression was defined by patients with initial Gleason 3+3 = 6 to any Gleason 4, and Gleason 3+4 = 7 to a primary Gleason 4 or higher. MRI progression was defined as increase in suspicion score, size, or new lesion on follow-up. PSA velocity (PSAV) &gt; 0.75ng/ml/yr, PSA doubling time (PSAdt) &lt; 3 yrs, and imaging characteristics were examined for association with pathologic progression at surveillance biopsy. Results: A total of 164 men, median age of 63 yrs [58-67], were included. Median length of follow up was 19.4 months [IQR 14.3-30.0]. Median PSA, and prostate volume of our cohort were 4.9ng/ml [3.3-7.3] and 47.0ml [36.5-59.8]. The sensitivity and specificity of predicting pathologic progression by mpMRI, PSAV and PSAdt were 45% and 65%, 30% and 76%, and 17% and 86% respectively. A combination of MRI, and PSAV or PSAdt yielded a sensitivity and specificity of 61% and 49% or 54% and 56% respectively. Using a decision curve analysis, mpMRI offers minimal benefit for predicting pathologic progression of CaP. Conclusions: MpMRI alone marginally outperforms PSA kinetics for predicting pathologic progression in men on AS for CaP. The combination of mpMRI along with PSA parameters increase the sensitivity of prostate imaging in identifying progression in AS patients. Research in combinations of imaging with other biomarkers will be needed to more accurately risk stratify AS patients.
Prospective study of tumor suppressor gene (TSG) methylation as a prognostic biomarker in surgically resected non-small cell lung cancer (NSCLC).
Authors: Christopher G. Azzoli, Alexander Edward Dela Cruz Drilon, Hirofumi Sugita, Camelia S. Sima, Eric Huang, Peter V. Danenberg, Mark G. Kris, Valerie W. Rusch
Journal: Journal of Clinical Oncology (2012)

7066 Background: In the New England Journal of Medicine, Brock et al. (2008) published a nested case-control study which tested the association between early recurrence of NSCLC after surgical resection, and TSG promoter methylation in tumor and lymph nodes detected by methylation-specific PCR (MSP). They reported that promoter methylation of the TSGs p16, CDH13, RASSF1A, and APC was significantly associated with early recurrence in 51 patients with stage I NSCLC compared to matched patients without early recurrence. We attempted to confirm these findings. Methods: In a prospective study, fresh frozen tumor tissue was acquired after surgical resection in 107 patients with stage I-IIIA NSCLC between 2003-2008. The promoter methylation status of the same 4 genes examined by Brock, et al (p16, CDH13, RASSF1A, APC), as well as 6 additional TSGs (MGMT, WIF-1, METH-2, GSTP1, SOCS3, DAPK) were assessed in the tumor tissue using quantitative MSP (MethyLight assay), with any amount of methylation scored as positive. Methylation status was correlated with clinical features, pathologic stage, disease-free survival (DFS), and overall survival (OS). Results: No significant associations were observed between promoter methylation of individual TSGs and DFS. No significant associations were observed between the number of methylated TSGs and DFS, or OS. Increased RASSF1A methylation was observed in poorly-differentiated and undifferentiated tumors compared to tumors that were well- or moderately-differentiated (p=0.031). Increased WIF-1 methylation and GSTP1 methylation were associated with increasing T (p=0.01) and N stage (p=0.028), respectively. Squamous cell carcinomas (SQCCs) were characterized by increased p16 methylation (p=0.0314) and decreased APC methylation (p=0.0146) compared to tumors of non-SQCC histologies. Conclusions: In this prospective study, we did not confirm that the promoter methylation of p16, CDH13, RASSF1A, and APC, or 6 other TSGs, was prognostic for early recurrence in surgically resected NSCLC.
Analysis of tumor immune protein expression and clinical outcomes in gastric adenocarcinoma.
Authors: Andrew M. Blakely, Andres Matoso, Thomas J. Miner
Journal: Journal of Clinical Oncology (2017)

177 Background: Up- and down-regulation of various immunomodulating proteins may reflect gastric tumor aggressiveness, possibly correlating with disease progression. Although a growing focus of investigation, literature is still lacking on which proteins may be predictors of patient outcomes. Methods: Retrospective review of a prospective database was performed of patients who underwent gastrectomy for adenocarcinoma with curative intent, 2003 to 2013. Patient demographics, operative details, pathology data, and outcomes were captured. Results: 86 of 105 gastrectomy patients had sufficient tissue for microarray analysis. Patients were mostly males (65.1%); median age was 74 years. 31 patients (36.0%) underwent total gastrectomy; the remainder underwent subtotal resection. 59 specimens (68.6%) had ≥ 15 lymph nodes harvested. Median tumor size was 4.9 cm; 55 (64.0%) were at least stage T3 and 63 (73.3%) had nodal involvement. 13 margins (15.1%) were positive, 50 had lymphovascular invasion (LVI, 58.1%), and 43 had perineural invasion (PNI, 50.0%). Median follow-up was 43 months; 28 patients (32.6%) died in follow-up. 9 patients (10.5%) developed local recurrence while 27 (31.4%) had regional/distant recurrence; median time to recurrence was 12 months. Recurrence was associated with LVI (50.0% vs. 25.0%, p = 0.028) and PNI (53.5% vs. 30.2%, p = 0.029). LVI was associated with microsatellite instability (MSI) (70.0% vs. 20.0%, p = 0.021). PNI was associated with suppressed programmed death-ligand 1 (PD-L1) expression in epithelium (73.1% vs. 41.4%, p = 0.0072) and lymphocytes (60.0% vs. 37.1%, p = 0.038). PD-L1 positive lymphocytes were associated with positive margins (21% vs 2%, p = 0.004). Epithelial indoleamine dioxygenase (IDO) expression was associated with lower recurrence (30.0% vs. 57.1%, p = 0.012). Conclusions: Histopathologic analysis of gastric cancer specimens may help identify which patients are more likely to develop recurrent disease. Downregulation of immunosuppressive proteins such as PD-L1 and IDO and MSI suggest more aggressive tumor biology. Knowledge of tumor protein expression profiles could be used to tailor adjuvant therapy to improve long-term oncologic outcomes.
Mental workload classification with concurrent electroencephalography and functional near-infrared spectroscopy
Authors: Yichuan Liu, Hasan Ayaz, Patricia A. Shewokis
Journal: Brain-Computer Interfaces (2017)

A brain-computer interface that measures the mental workload level of operators has applications in human-computer interactions (HCI) for reducing human error and improving work efficiency. In this study, concurrently recorded electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) were combined at the decision fusion stage for the classification of three mental workload levels induced by an n-back working-memory task. An average three-class classification accuracy of 42, 43, and 49% has been achieved across 13 participants for the fNIR-alone, EEG-alone, and EEG-fNIRS combined approach, respectively. The current study demonstrated a multimodality-based approach to decode human mental workload levels that may potentially be used for adaptive HCI applications.
Using quantitative sensory testing as an early predictor of chronic oxaliplatin neuropathy in gastrointestinal cancer patients.
Authors: Sangeetha Meda Reddy, Nancy Kwon, Irene B. Helenowski, Robert Norm Harden, Judith A. Paice, Halla Sayed Nimeiri, Mary Frances Mulcahy, Al B. Benson, Maxwell Thomas Vergo
Journal: Journal of Clinical Oncology (2013)

3540 Background: Acute oxaliplatin neurotoxicity has been shown to be predictive of chronic neuropathy, a devastating irreversible adverse effect of oxaliplatin. Our study was designed to test the utility of quantitative sensory testing (QST) to measure acute oxaliplatin neurotoxicity at early time points to identify those at risk for developing chronic neuropathy. Methods: Gastrointestinal cancer patients receiving 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy were evaluated over a 1 year period for development of acute and chronic oxaliplatin neurotoxicity: before starting FOLFOX, 1 hour into oxaliplatin infusion, before cycles 2, 4 and 12, and 1 year after start of treatment. Patients underwent QST to measure thermal and mechanical sensitivities, vibration detection, pain sensation, and fine motor skills. Chronic neuropathy was measured using National Cancer Institute Common Toxicity Criteria for Adverse Events version 4. Results: We conducted analysis of 18 patients that have reached the 1 year followup period. We found thermal QST measured during cycle 1 infusion, which is indicative of acute neurotoxicity, to be predictive of 1 year neuropathy. Decreased cold detection intrainfusion during cycle 1 relative to baseline scores yielded a significant correlation to chronic neuropathy scores (rs= -0.53, p=0.03) and predicted grade 2 or 3 neuropathy (p=0.048). Furthermore, decreased cold detection scores intrainfusion showed trend towards correlation to neuropathy scores (rs= -0.45, p=0.07) and prediction of grade 2 or 3 neuropathy (p=0.07). Additionally, patients with higher tolerance to cold and heat intrainfusion were at higher risk for grade 1 or higher neuropathy (p=0.057 for cold pain, p=0.03 for heat pain). We also found decreased mechanical detection scores using von frey filaments as early as cycle 2 were correlated to 1 year neuropathy scores (rs=0.52, p=0.03) and predicted development of grade 2 or 3 neuropathy (p=0.008). Conclusions: We can use QST to identify high risk patients that are likely to develop chronic neuropathy at 1 year, allowing for targeted use of preventive measures to decrease the incidence of this debilitating adverse effect.
Prostate cancer meta-analysis from more than 145,000 men to identify 65 novel prostate cancer susceptibility loci.
Authors: Rosalind Eeles, Ali Amin Al Olama, Sonja Berndt, Fredrik Wiklund, David V Conti, Mahbubl Ahmed, Sara Benlloch, Douglas Easton, Peter Kraft, Stephen J. Chanock, Zsofia Kote-Jarai, Christopher Haiman, Fredrick R Schumacher
Journal: Journal of Clinical Oncology (2017)

1 Background: Currently genome-wide association studies (GWAS) have identified over 100 prostate cancer (PrCa) susceptibility loci, capturing 33% of the PrCa familial relative risk (FRR) in Europeans. To identify further susceptibility variants, we conducted a PrCa GWAS, larger than previous studies, comprising ~49,000 cases and ~29,000 controls among individuals of European and Asian descent using the OncoArray, a platform consisting of a 260K GWAS backbone and 310K custom content selected from previous GWAS and fine-mapping studies of multiple cancers ( http://epi.grants.cancer.gov/oncoarray/ ). Methods: Genotypes from the OncoArray were used to impute genotypes from ~70M variants using the October 2014 release of the 1000 genomes project as a reference, and then combined with several previous PrCa GWAS of European ancestry: UK stage 1 (1,906 cases/1,934 controls) and stage 2 (3,888 cases/3,956 controls); CaPS 1 (498 cases/502 controls) and CaPS 2 (1,483 cases/519 controls); BPC3 (2,137 cases/3,101 controls); NCI PEGASUS (4,622 cases/2,954 controls); and iCOGS (21,209 cases/ 20,440 controls). Risk analyses for overall PrCa risk, aggressive PrCa (several definitions defined by PrCa clinical characteristics), and Gleason score were performed. Logistic and linear regression summary statistics were meta-analysed using an inverse variance fixed effect approach. Results: We identified novel loci significantly associated ( P &lt; 5.0x10 -8 ) with overall PrCa (N = 65). Our novel findings are comprised of several missense variants, including a SNP in the ATM gene - a key member of the DNA repair pathway. When combined multiplicatively, the 65 novel PrCa loci identified here increases the captured heritability of PrCa, explaining 38.5% of the FRR when combining novel and previously identified PrCa loci. Conclusions: In risk stratification, men in the top 1% of the genetic risk score group have a relative risk of 5.6 fold for developing PrCa compared with the median risk group. These results will improve the utility of genetic risk scores for targeted screening and prevention for prostate cancer.
Response to Comment on Gastaldelli et al. Short-term Effects of Laparoscopic Adjustable Gastric Banding Versus Roux-en-Y Gastric Bypass. Diabetes Care 2016;39:1925–1931
Authors: Amalia Gastaldelli, Francesco Rubino, Geltrude Mingrone
Journal: Diabetes Care (2017)

We would like to thank Drs. Algahim and Taegtmeyer for their comments (1) on our article (2). We agree that in the long term a significant weight loss, such as that obtained after bariatric/metabolic surgery, can surely contribute to the improvement of insulin sensitivity. Nonetheless, although in our series both gastric banding and Roux-en-Y gastric bypass (RYGB) led to significant improvement in hepatic insulin sensitivity, endogenous glucose production, and lipolysis, only RYGB improved insulin sensitivity of …
Clinical analysis of multiple primary cancers
Authors: K. Lee, H. Jang, M. Choi, J. Kong, S. Lee, J. Kwon, E. Nam, Y. Mun, C. Seong, S. Lee
Journal: Journal of Clinical Oncology (2007)

19639 Background: Multiple primary cancers are defined as two or more abnormal growths of tissue occurring simultaneously or abnormal growths of tissues that follow a previous neoplasm but are not metastases of the latter in the same individual. The primary objective of this study was to determine the occurrence, clinical characteristics and prognosis of multiple primary cancers in single institution, respectively. Methods: Between January 1995 and June 2006, patients with multiple primary cancers were selected from a review of patients who had been treated and followed-up in our Ewha Womans University Hospital. Demographic data were obtained from medical records. Results: Two hundred seven patients were selected and patients with multiple primary cancers constituted 1.95% of all malignancies. Male to female ratio was 1.84. (male 134 vs. female 73 patients) The median age first cancer diagnosis was 67 years old in male, 57 in female. The incidence of synchronous cancers is higher than metachronous. (108 vs. 99) and the median time to additional cancers in metachronous group was 35 months. The most frequent cancers was gastrointestinal cancers in both sex synchronously and metachronously. In male, colorectal cancer followed by gastric cancer methchronously (9.1%), genitourinary cancer with another genitourinary cancer synchronously (12.7%) were frequently observed. In female, breast cancer followed by colorectal cancer metachronously (6.8%), gastric cancer with colorectal cancer (6.9%) were frequently observed. The median survival duration was 14.4 months totally from the index diagnosis and synchronous cancers showed lower survival duration than metachronous cancers. (7.4 vs. 26.1 months, p=0.017) Conclusions: Adequate investigations including G-I tract should focus in the first 3 years after initial diagnosis to detect second primary cancers earlier. No significant financial relationships to disclose.