tbuckley/cabot-search huggingface dataset:
Prognostic significance of urinary neopterin in ovarian cancer a study of the Austrian Gynecologic Oncology Group.
Authors: Christian Marth, Birgit M Volgger, Gudrun Windbichler, Alain G Zeimet, Anton Graf, Gerhard Bogner, Lukas Angleitner-Boubenizek, Ursula Denison, Michael Rohde, Gerhard Sliutz, Lothar Fuith, Dietmar Fuchs
Journal: Journal of Clinical Oncology (2014)

5561 Background: Neopterin is produced by activated macrophages upon stimulation with interferon-gamma (IFN-g) and thus elevated concentrations in patients indicate cellular immune response. Most studies in patients with malignant diseases found an association between higher neopterin concentrations with reduced survival and impaired prognosis, although it is not a classical tumor marker since it is not produced by cancer cells. Methods: In a study of the Austrian Gynecologic Oncology Group in 114 patients with cystadenomas and 17 patients with borderline ovarian tumors as well as 223 invasive ovarian cancer patients urinary neopterin was determined before and after primary therapy. Results: Elevated levels (cutoff 250 µmol/mol creatinine) were found less frequently in women with benign ovarian cystadenomas (24%) and borderline tumors (29%) compared to patients with malignant disease. We observed stage dependency with 16%, 25%, 65% and 91% in FIGO stage I-IV, respectively. By univariate analysis residual tumor, FIGO stage, age, histological type, and neopterin was significantly associated with overall and progression-free survival (OS and PFS). Median OS was 81 versus 24 months for patients with normal and elevated neopterin, median PFS was 52 and 12 months respectively (p<.001 for both). In a multivariate Cox regression analysis, residual tumor, neopterin and age were independently associated with OS, while only residual tumor was predictive for PFS. Thirty patients with surgically staged FIGO I or II invasive ovarian cancer were analyzed separately. Two of three patients with elevated levels died of disease in contrast to 2/27 deaths in women with normal neopterin (p=.004, Fisher's exact test). Conclusions: In ovarian cancer the negative impact of pretreatment urinary neopterin indicates a detrimental role of immune activation for the course of the disease.
A novel gene signature to predict distant metastasis in stage I lung cancer patient following local therapy with surgery or stereotactic body radiation therapy (SBRT).
Authors: Sungjune Kim, Dung-Tsa Chen, Abdullah Faisal Al-Rashdan, Rasha Elsaka, Lary Robinson, Eric B. Haura, Javier Torres-Roca, Thomas J. Dilling, Craig William Stevens
Journal: Journal of Clinical Oncology (2014)

7538 Background: The standard management for stage I non-small cell lung cancer is surgical resection and SBRT. Adjuvant therapy is typically not given in this group of lung cancer patients. Unfortunately, 14% to 23% who undergo surgery for a stage I NSCLC ultimately fail distantly. Methods: Moffitt Cancer Center (MCC) has launched a major initiative termed Total Cancer Care (TCC) to innovate personalized compiling 40,000 tumor microarray databank linked to longitudinal clinical data. We conducted a retrospective chart review of pathologic T1-T2N0 NSCLC patients in the TCC database, and classified patients according to their recurrence pattern. CEL files from Affymetrix microarray from pathologic specimens from these patients were obtained from TCC, and gene expression profile was analyzed. Results: We identified a cohort of 143 patient treated with surgical resection. 56 patients were without evidence of disease at least 3 years following surgery (Control cohort), 34 patients failed locally and in regional lymph nodes (Loco-regional failure cohort), and 53 patients developed distant metastasis (distant failure cohort). 144 genes were identified that showed significant differences in RNA expression level between control cohort vs. distant failure cohort. However, only 1 gene was associated with loco-regional failure. 144 genes identified were validated against the Director’s Challenge database. Over 90% of the genes identified from this study correctly predicted survival outcome from the Director’s Challenge database. Conclusions: We have identified a group of genes that predict distant metastasis among surgically resected pathologic T1-T2N0 adenocarcinoma of the lung. We are currently developing the scoring system to classify this earliest stage lung adenocarcinoma patients into 3 groups, low risk, intermediate risk, and high risk for distant failure based on our gene signature. The outcome of this study will identify a select group of stage I lung adenocarcinoma patients who will benefit from adjuvant chemotherapy after local therapy with surgery or SBRT. Ultimately, we are planning to translate these findings to a clinical trial.
Results of Off-Label Venetoclax Use in Combination with Low-Intensity Chemotherapy in Patients with Relapsed and Refractory Myeloid Malignancies
Authors: Caitlin R Rausch, Courtney D. DiNardo, Tapan Kadia, Koichi Takahashi, Nitin Jain, Christopher B Benton, Philip A Thompson, Maro Ohanian, Wendy Covert, Morgan Mace, Kayleigh Marx, Naveen Pemmaraju, Naval Daver, Elias J. Jabbour, Jorge E. Cortes, Guillermo Garcia-Manero, Farhad Ravandi, Marina Konopleva, Hagop M. Kantarjian
Journal: Blood (2017)
Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors
Authors: K.M. Heinhuis, W. Ros, M. Kok, N. Steeghs, J.H. Beijnen, J.H.M. Schellens
Journal: Annals of Oncology (2019)

Cancer immunotherapy has changed the standard of care for a subgroup of patients with advanced disease. Immune checkpoint blockade (ICB) in particular has shown improved survival compared with previous standards of care for several tumor types. Although proven to be successful in more immunogenic tumors, ICB is still largely ineffective in patients with tumors that are not infiltrated by immune cells, the so-called cold tumors.
Possibilities of complex sonography in children with pelvic tumors.
Authors: Natalia A. Maksimova, Yuliya Yu. Kozel, Maria G. Ilchenko, Sergei A. Kuznetsov, Gulnara A. Mkrtchyan, Maria V. Starzhetskaya
Journal: Journal of Clinical Oncology (2014)

e21015 Background: Pelvic tumor is a rare pathology, it comes to 0,5-2% of general structure of cancer incidence in children. Timely and accurate diagnosis of these tumors remains one of relevant and insufficiently explored problems in pediatric oncology. The purpose of the study was to specify possibilities of complex sonography in children with pelvic tumors. Methods: 73 children with pelvic malignancies were recruited, the majority of them with germ cell tumors, sex cord-stromal tumors, gonadoblastomas - 44 patients (60%), 43 (97,7%) of them in girls. Rhabdomyosarcoma was observed in 17 (23%) children, in boys and girls equally. 4 (9%) patients had neuroblastoma and 1 - primitive neuro-ectodermal tumor. Complex ultrasonic scanning of organs of the abdominal cavity and the pelvic cavity was performed with IU 22 PHILIPS ultrasound system with the use of 2-5 MHz convex broadband transducer. The scanning was performed by the standard method in B-mode, in color and power Doppler with a Doppler phase. Results: As a result of the study, typical ultrasound signs of pelvic malignancies regardless histological structure were determined: irregular shape – 39 (88,6%), inhomogeneous structure – 41 (93,2), irregular blurred contours – 37 (84%), cystic abnormalities – 28 (63,6%), calcifications – 15 (34%). In dopplerography intense intratumoral blood flow was registered, arterial mostly – 40 (90,9%) with the range of maximum arterial speeds from 12,5 to 45 cm/sec, average maximum arterial speed = 30 cm/sec. Accuracy of the method amounted to 87%, sensitivity 85%, specificity 86,2%. Conclusions: Thus, complex sonography is important in primary diagnosis of pelvic tumors in children, it helps to determine the localization and extension of tumor as well as to plan further examination and treatment of patients.
Abstract O.43: Partial and Complete Non-response to Intravenous Immunoglobulin in the Acute Treatment of Kawasaki Disease: A Matched Case-control Study
Authors: Mallory L Downie, Cedric Manlhiot, Giuseppe A Latino, Tanveer H Collins, Nita Chahal, Rae S Yeung, Brian W McCrindle
Journal: Circulation (2015)

Introduction: Patients non-responsive to intravenous immunoglobulin (IVIG) in the acute phase of Kawasaki disease (KD) are usually considered a single patient group; however, response to second-line therapy varies significantly. We sought to characterize the pattern of temperature response to IVIG infusion, and to define whether the profile was associated with response to second-line therapy in non-responders. Methods: Patients non-responsive to IVIG (temperature &gt;37.5°C &gt;24 hours after the end of IVIG) were identified. Each IVIG non-responder was matched to a IVIG-responsive control patient of the same age and gender, and with the same duration of fever prior to IVIG. Hourly temperature profiles were obtained from immediately before the start of the IVIG infusion until complete defervescence. Results: n=202 patients non-responsive to IVIG were matched (total n=404). For all, temperature reduced by 0.17 (0.06)°C per g/hr IVIG (p=0.006). Important variation in the temperature profile was noted for patients who did not defervesce with IVIG. Thus, non-responders were further classified as partial non-responders (31%) (temperature decreased to &lt;37.5°C within 24 hours of the end of IVG infusion, but fever recurred) and complete non-responders (69%) (temperature consistently &gt;37.5°C throughout IVIG treatment). The temperature profile during IVIG infusion was similar between complete and partial responders [(EST: -0.26 (0.11)°C per g/hr IVIG (p=0.02) for complete responders vs. EST: -0.20 (0.09)°C (p=0.02) for IVIG responders (responders vs. partial non-responders, p=0.65)]. In complete non-responders, IVIG was not associated with significant decreases in temperature (EST: -0.11 (0.14)°C, p=0.43). Factors associated with complete (vs. partial) non-response included presence of infectious symptoms, differences in multiple laboratory values and IVIG brand. Defervescence in partial non-responders was achieved with a second IVIG dose for 88% of patients compared to only 47% of complete non-responder (p&lt;0.001). Conclusions: Non-response to initial IVIG can be further characterized by the temperature profile, and complete non-responders may require more aggressive second-line therapy.
Initial experience of combined use of PDD and NBI for detection for flat urothelial lesion.
Authors: Yoshio Naya, Fumiya Hongo, Terukazu Nakamura, Masakatsu Oishi, Takashi Ueda, Kazumi Kamoi, Koji Okihara, Tsuneharu Miki
Journal: Journal of Clinical Oncology (2014)

e15511 Background: PDD or NBI is useful for detection of CIS. There is no paper to compare the diagnostic power of PDD with that of NBI in same patients. This study is conducted for comparison PDD with NBI in same patients with flat urothelial lesion suspicious of CIS. Methods: In Japan, PDD has just been approved as advanced medical technology in registered institutions by the Ministry of Health, Labor, and Welfare in 2010, and this study was conducted for registration of advanced medical technology. ALA-PDD was approved by the ethics committees of our institution in November 2012 for 10 patients with NMIBC. Between November 26, 2012 and April 1, 2013, 10 patients with CIS suspected underwent TURBt using PDD and NBI in same time. The bladder was mapped first under white light (WL) and then under NBI, and afterwards under blue light in patients with odd number. The bladder was mapped first under WL and then under blue light, and afterwards under NBI in patients with even number. Biopsies were carried out from all suspicious areas noting if lesions were detected by NBI or PDD. Random cold cup biopsies from healthy mucosa of bladder were performed from negative lesions of PDD and NBI. Results: The sensitivity and specificity for detection CIS and dysplasia were 0.916 and 0.827 in PDD and 0.625 and 0.879 in NBI, respectively. Cancer was detected from 12 lesions. Overall the suspicious lesions were 22 in the NBI and 32 in the PDD. Of 22 lesions in NBI, pathological examination revealed 9 CIS lesions and 6 dysplastic lesion, respectively. Of 32 lesions in PDD, pathological examination revealed 12 cancerous lesions, and 10 dysplastic lesions respectively. There was no cancer in 50 lesions with PDD negative. Twelve cancerous lesions were all PDD positive and 3 (25%) of 12 cancerous lesions missed in NBI. Of 12 dysplatic lesions, 10 lesions (83.3%) were PDD positive and 8 lesions (66.7%) were NBI positive (p = 0.028). There were no cancer and dysplasia in 43 lesions both PDD and NBI negative. Conclusions: When the finding under PDD was negative, the possibility for CIS might be very low, and when both PDD and NBI were negative, the possibility for CIS or dysplasia might be very low. The efficacy of PDD and usefulness of the combination PDD with NBI was suggested in this study.
Tyrosine-kinase inhibitors (TKI) in metastatic kidney cancer (mKC) treatment.
Authors: Liubov Yu Vladimirova, Oleg Ivanovich Kit, Irina L Popova, Natalya A Abramova
Journal: Journal of Clinical Oncology (2014)

e15546 Background: Kidney cancer is one of the most chemotherapy resistant tumors. Targeted drugs allows to improve the treatment efficacy. This study was carried out to evaluate the safety and efficacy of TKI Pazopanib (P) and Sunitinib (S) for mKC. Methods: Elegibility criteria included measurable mKC T2-4N0-2M0-1, ECOG ≤ 2, adequate hepatic, renal and bone marrow functions, no brain metastases. P was administrated 800 mg per day. S was administrated 50 mg per day. The frequency of response rate (RR), OS, PFS and safety were evaluated. Duration of therapy was mean time 6,4±1,3 mos (3-10 mos). Results: 15 patients (12 men, 3 women), mean age 59,7±5,3 yrs were recruited. 26.6%(4) patients had a primarily mKC and 73.3%(11) had with progression after radical treatment. 10 (66.6%) had multiple synchronous metastases. 10 (66.6%) patients received P, 5 (33.3%) received S. Disease control was 80.0% (12) including 33.3% PR (5), in 46.7% SD(7). OS was 15.3±2.5mos, PFS - 6.2±1.9mos. 13 patients (86.6%) are alive for the time of abstract. Common toxicities were: hand-foot syndrome 1/2Gr - 5(33.3%), 3Gr hypertension - 5(33.3%), arthralgia 1/2Gr - 2(13.3%), thrombocytopenia - 3 (20%) including 1Gr 2 patients and grade 3Gr - 1, diarrhea 2/3Gr - 4(26.6%). All toxicities were controlled by symptomatic medication if necessary, didn't require dose reduction and discontinuation. Conclusions: TKI therapy is an optimal method of treatment for mKC.
Liver-directed therapies for colorectal cancer liver metastasis (CLRM): A Surveillance, Epidemiology, and End Results (SEER)-Medicare analysis.
Authors: Muhammad Shaalan Beg, Faisal Adhami, Lei Xuan, Joseph Hodges, Jeffery Meyer, Ethan Halm, Sandi Pruitt
Journal: Journal of Clinical Oncology (2014)

577 Background: Oligometastatic CLRM comprises a distinct subset of stage IV colorectal cancer. Liver directed therapies (LDT) including surgery, ablation, radiation, and transarterial chemotherapy/embolization have been shown to improve cancer outcomes in smaller series. We sought to evaluate utilization of LDT and their impact on survival in patients with CLRM in a population-based database. Methods: We analyzed linked SEER-Medicare data. Eligible patients were ≥ 66 years, diagnosed between 1992-2009, carry a code for secondary malignancy of the liver (ICD-9 197.7) and survived ≥ 30 days after diagnosis. LDT (yes vs. no) were defined by ICD-9 and CPT codes of surgery (hepatectomy), ablation (e.g. radiofrequency and cryoablation), radiation (e.g., stereotactic surgery and brachytherapy), and transarterial/embolization (e.g., radioembolization). Treatment and non-treatment groups were matched using a propensity score comprised of a comprehensive set of patient and tumor characteristics including: age, sex, race, marital status, Medicaid status, and tumor histology, grade, and location. Cox Proportional Hazard models were used to compare the impact of the LDT on overall survival among propensity-matched pairs of treated and untreated patients. Results: LDT were performed in 12.7% (n = 1,793) of all 14,150 patients. There were 13.7% of patients over 85 years. Females were 52.1% and 83 % White. Off all, 5.4% had surgery, 3.9% had ablation, 4.6% had radiation, and 1.6% had transarterial chemotherapy/embolization. Unadjusted 5 year overall-survival (OS) was 26.9% for those underdoing LDT vs. 7.5% who did not (HR = 0.44, (CI 0.41,0.46)). Cox modeling demonstrated a survival benefit for each LDT with HR of 0.36 (0.33,0.39) for surgery, 0.35 (0.32,0.39) for ablation, 0.78 (0.72, 0.85) for radiation and 0.42 (0.36,0.49) for transarterial/embolization. Conclusions: While use of LDT for CLRM in this national sample of Medicare patients were low, those who received treatment had markedly improved survival compared to matched patients who did not. Surgery and ablation were the most effective therapies. These findings require evaluation in a prospective clinical study.
Association of Combined Modality Therapy vs Chemotherapy Alone With Overall Survival in Early-Stage Pediatric Hodgkin Lymphoma
Authors: Sachin R. Jhawar, Zorimar Rivera-Núñez, Richard Drachtman, Peter D. Cole, Bradford S. Hoppe, Rahul R. Parikh
Journal: JAMA Oncology (2019)

To date, there is no well-defined standard of care for early-stage pediatric Hodgkin lymphoma (HL), which may include chemotherapy alone or combined modality therapy (CMT) with chemotherapy followed by radiotherapy. Although the use of radiotherapy in pediatric HL is decreasing, this strategy remains controversial.To examine the use of CMT in pediatric HL and its association with improved overall survival using data from a large cancer registry.This observational cohort study used data from the National Cancer Database to evaluate clinical features and survival outcomes among 5657 pediatric patients (age, 0.1-21 years) who received a diagnosis of stage I or II HL in the United States from January 1, 2004, to December 31, 2015. Statistical analysis was conducted from May 1 to November 1, 2018.Patients received definitive treatment with chemotherapy or CMT, defined as chemotherapy followed by radiotherapy.Kaplan-Meier survival curves were used to examine overall survival. The association between CMT use, covariables, and overall survival was assessed in multivariable Cox proportional hazards regression models. Use of radiotherapy was assessed over time.Among the 11 546 pediatric patients with HL in the National Cancer Database, 5657 patients (3004 females, 2596 males, and 57 missing information on sex; mean [SD] age, 17.1 [3.6] years) with stage I or II classic HL were analyzed. Of these patients, 2845 (50.3%) received CMT; use of CMT vs chemotherapy alone was associated with younger age (<16 years, 1102 of 2845 [38.7%] vs 856 of 2812 [30.4%]; P < .001), male sex (1369 of 2845 [48.1%] vs 1227 of 2812 [43.6%]; P < .001), stage II disease (2467 of 2845 [86.7%] vs 2376 of 2812 [84.5%]; P = .02), and private health insurance (2065 of 2845 [72.6%] vs 1949 of 2812 [69.3%]; P = .002). The 5-year overall survival was 94.5% (confidence limits, 93.8%, 95.8%) for patients who received chemotherapy alone and 97.3% (confidence limits, 96.4%, 97.9%) for those who received CMT, which remained significant in the intention-to-treat analysis and multivariate analysis (adjusted hazard ratio for CMT, 0.57; 95% CI, 0.42-0.78; P < .001). In the sensitivity analysis, the low-risk cohort (stage I-IIA) and adolescent and young adult patients had the greatest benefit from CMT (adjusted hazard ratio, 0.47; 95% CI, 0.40-0.56; P < .001). The use of CMT decreased by 24.8% from 2004 to 2015 (from 59.7% [271 of 454] to 34.9% [153 of 438]).In this study, pediatric patients with early-stage HL receiving CMT experienced improved overall survival 5 years after treatment. There is a nationwide decrease in the use of CMT, perhaps reflecting the bias of ongoing clinical trials designed to avoid consolidation radiotherapy. This study represents the largest data set to date examining the role of CMT in pediatric HL.
Argininosuccinate synthetase 1 (ASS1) expression and response to arginine deprivation with ADI-PEG20 in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC).
Authors: Jason Howard, Jimena Perez, Robbert Slebos, Christine H. Chung
Journal: Journal of Clinical Oncology (2014)

e17041 Background: Proteomic studies determined that ASS1, the metabolic enzyme which catalyzes the penultimate step of arginine biosynthesis, is differentially expressed in HNSCC tumors with respect to HPV status. Pegylated arginine deiminase (ADI-PEG20) reduces extracellular arginine, and consequently nitric oxide (NO) production which is known to trigger apoptosis in tumors with low ASS1 expression. We evaluated the sensitivity of HNSCC cell lines to ADI-PEG20 and correlated response with ASS1 expression. Methods: ThreeHPV+ (UPCI-SCC90, UMSCC47, 93VU147T) and four HPV- (SCC15, SCC25, FaDu, SCC61) HNSCC cell lines were treated with various concentrations of ADI-PEG20 or in combination with cisplatin or docetaxel. Effects of drug treatment on proliferation and clonogenicity were determined using Matrigel colony formation assay. ASS1 expression was also determined by Western blot analysis. ADI-PEG20 and anti-ASS1 antibody were kindly provided by Polaris Pharmaceuticals. Results: ADI-PEG20 decreased proliferation in all seven HNSCC cell lines as determined by average colony size in Matrigel growth assays; however, only the HPV+ cells demonstrated a significant decrease in clonogenicity. Additionally, 93VU147T was moderately sensitive to ADI-PEG20, but added benefit was achieved when this agent was combined with docetaxel. When HNSCC cell lines were evaluated for ASS1 expression by Western blot analysis, HPV- ASS1 expression did not correlate with ADI-PEG20 sensitivity, however ASS1 levels correlated with the clonogenic response of the HPV+ cell lines. Conclusions: ADI-PEG20 inhibits proliferation in HNSCC and is potentially synergistic in combination with docetaxel in HPV+ cells. Low ASS1 expression may serve as a biomarker for ADI-PEG20 sensitivity in HPV+ HNSCC. These results support further in vivo studies to determine the clinical potential of ADI-PEG20 in management of HNSCC.