tbuckley/cabot-search huggingface dataset:
Prevalence of late morbidity in survivors of Hodgkin’s lymphoma (HL) treated during adulthood
Authors: M. J. Matasar, J. N. Butos, L. N. McCallen, E. R. Riedel, J. S. Ford, D. M. Weinstock, K. C. Oeffinger, D. J. Straus
Journal: Journal of Clinical Oncology (2008)

9589 Background: There exists a growing understanding of the late effects of treatment of children with HL. In contrast, the global burden of late morbidity among long-term survivors of adult-onset HL and factors associated with late morbidity remain poorly characterized. Methods: We conducted a survey-based cohort study of patients treated as adults on first-line therapy protocols for HL at our center from 1975–2000. The protocols included 5 combined modality trials of chemotherapy (CT) + radiation therapy (RT) and one that included a CT- only arm. Late health conditions were assigned severity scores based on a modification of the Common Terminology Criteria for Adverse Events, version 3 (grades 1 to 4 describing the range from mild to life-threatening or disabling). The Mantel-Hanzel test for trend was used to assess associations between health conditions and patient and treatment characteristics. Results: Of 707 pts for whom follow-up was available, 514 were alive; median survival was 29y. Survey data were available for 186 pts, with a median time from last treatment of 21y. Median age at interview was 48y (range, 25–88) and median age at treatment initiation was 30y (range, 14–66). 52% were women, and 96% were white non-Hispanic. Remarkably, 94% of respondents reported at least one condition, and 50% reported at least 1 condition that was grade 3 or greater. Multiple late morbidities were frequently reported: 23% reported 2 or more grade 3 or 4 conditions, and 5% 3 or more grade 3 or 4 conditions. Age at first treatment, time from last treatment, and RT dose were associated with the prevalence of certain conditions: Younger age at treatment was associated with greater prevalence of endocrine (p=0.04) and psychiatric (p=0.001) conditions; longer followup with second malignancies (p=0.02), cardiovascular (p=0.02), musculoskeletal (p=0.001), and endocrine (P=0.001) disorders; and increasing RT dose with endocrine (p=0.003) and psychiatric (p=0.02) dysfunction. Conclusions: Late morbidity is nearly universal among survivors of HL treated as adults. Evidence-based guidelines built upon such data are needed to aid clinicians in the management of survivors of HL. No significant financial relationships to disclose.
Analysis of matched case-control studies
Authors: Neil Pearce
Journal: BMJ (2016)

There are two common misconceptions about case-control studies: that matching in itself eliminates (controls) confounding by the matching factors, and that if matching has been performed, then a "matched analysis" is required. However, matching in a case-control study does not control for confounding by the matching factors; in fact it can introduce confounding by the matching factors even when it did not exist in the source population. Thus, a matched design may require controlling for the matching factors in the analysis. However, it is not the case that a matched design requires a matched analysis. Provided that there are no problems of sparse data, control for the matching factors can be obtained, with no loss of validity and a possible increase in precision, using a "standard" (unconditional) analysis, and a "matched" (conditional) analysis may not be required or appropriate.
EBV-positive lymphoproliferative disease with medullar, splenic and hepatic infiltration after imatinib mesylate therapy for chronic myeloid leukemia with two relapses and rituximab resistance
Authors: T. Leguay, C. Foucaud, M. Parrens, O. Fitoussi, K. Bouabdallah, M. Belaud-Rotureau, R. Tabrizi, G. Marit, A. Pigneux, N. Milpied
Journal: Journal of Clinical Oncology (2007)

17536 Background: Imatinib mesylate has transformed the management of the patients with chronic myeloid leukemia (CML). Initially, few undesirable effects was described. In 2003, Bekkenk presented the first EBV-positive cutaneous B-cell lymphoproliferative disease during imatinib mesylate therapy with disappearance of the cutaneous tumor after interruption of the specific inhibitor of BCR-ABL. Methods: Results: We reported a case of first EBV-positive lymphoproliferative disease with diffuse infiltration. Our patient 59 years old female was treated with imatinib mesylate for CML in chronic phase. CML was diagnosed on 2003 and imatinib mesylate therapy (400 mg/day) was initiated. A CCR was achieved after six months and a major molecular response after eighteen months. EBV-positive lymphoproliferative disease was diagnosed on 2005 and interruption of imatinib mesylate have not demonstrated efficiency. A response was initially obtained after treatment with rituximab alone, but our patient relapsed after reintroduction of imatinib at the same dose. A retreatment with rituximab have permitted a second biological complete remission and disappearance of clinical abnormalities but during only few months. At the second relapse, the disease transformed into a CD20-negative diffuse large B cell lymphoma and became resistant to rituximab therapy. Nevertheless, the lymphoproliferative disease remained responsive to conventional chemotherapy with CHOP and Interferon-alpha. Conclusions: Imatinib mesylate has modified the evolution of CML with an improvement of overall survival. In vitro studies have shown that imatinib mesylate is able to inhibit the proliferation and the activation of T-cells, and to reduce significantly the antigen-triggered expansion of CD8+ T cells in response to immunodominant EBV peptides. We speculate that such an effect might have occurred in our patient. Despite a growing number of patient receiving this tyrosine kinase inhibitor, case reports of EBV-positive lymphoproliferation disease remain rare. No significant financial relationships to disclose.
Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo
Authors: Hatem A.F.M. Hassan, Lesley Smyth, Noelia Rubio, Kulachelvy Ratnasothy, Julie T.-W. Wang, Sukhvinder S. Bansal, Huw D. Summers, Sandra S. Diebold, Giovanna Lombardi, Khuloud T. Al-Jamal
Journal: Journal of Controlled Release (2016)

Carbon nanotubes (CNTs) have shown marked capabilities in enhancing antigen delivery to antigen presenting cells. However, proper understanding of how altering the physical properties of CNTs may influence antigen uptake by antigen presenting cells, such as dendritic cells (DCs), has not been established yet. We hypothesized that altering the physical properties of multi-walled CNTs (MWNTs)-antigen conjugates, e.g. length and surface charge, can affect the internalization of MWNT-antigen by DCs, hence the induced immune response potency. For this purpose, pristine MWNTs (p-MWNTs) were exposed to various chemical reactions to modify their physical properties then conjugated to ovalbumin (OVA), a model antigen. The yielded MWNTs-OVA conjugates were long MWNT-OVA (~ 386 nm), bearing net positive charge (5.8 mV), or short MWNTs-OVA (~ 122 nm) of increasing negative charges (− 23.4, − 35.8 or − 39 mV). Compared to the short MWNTs-OVA bearing high negative charges, short MWNT-OVA with the lowest negative charge demonstrated better cellular uptake and OVA-specific immune response both in vitro and in vivo. However, long positively-charged MWNT-OVA showed limited cellular uptake and OVA specific immune response in contrast to short MWNT-OVA displaying the least negative charge. We suggest that reduction in charge negativity of MWNT-antigen conjugate enhances cellular uptake and thus the elicited immune response intensity. Nevertheless, length of MWNT-antigen conjugate might also affect the cellular uptake and immune response potency; highlighting the importance of physical properties as a consideration in designing a MWNT-based vaccine delivery system.
Abstract 18342: Electrocardiographic Screening of One-month-old Infants with High Risk for Sudden Infant Death in Japan
Authors: Masao Yoshinaga, Yumiko Ninomiya, Yuji Tanaka, Kazuyuki Tanoue, Norito Nuruki, Masahiro Sonoda
Journal: Circulation (2012)

Backgrond: Sudden infant death syndrome (SIDS) is one of the major causes of death in infancy with the highest prevalence at about 2 months of age. Genetic studies have shown that about 10% of cases diagnosed as SIDS carry functionally significant mutations in long QT syndrome (LQTS) genes. In Japan, medical examinations at one month of age are performed for all infants currently. Aim: We assessed the hypothesis that electrocardiographic screening of one-month-old infants is able to screen infants with LQTS and those with risk of sudden death other than LQTS. Methods: The study was conducted in eight areas in Japan. Twelve-lead electrocardiograms were recorded and the QT/RR intervals of three consecutive beats were measured. Our prospective study showed that a formula to minimize the effect of heart rate for infants was QTc=QT/RR 0.43 and a provisional criterion of a QTc≥0.44 was appropriate. To assess the validity of the criterion, all infants with a QTc ≥0.43 were followed. Results: Of 4,319 infants who participated, 6 infants had a QTc value of ≥0.44 at one-month-old. From the follow-up ECGs, four infants were diagnosed as LQTS clinically. Two infants showed progress prolongation of the QTc intervals; propranolol and mexiletine were administered when their QTc values exceeded ≥0.50 0.43 . Genetic testing revealed a KCNH2 mutation (3065 delT, L1021fs+34X) in one of these two infants. Remaining two infants with a QTc ≥0.44 had been following without medication. All 10 infants with the QTc values between 0.43 and 0.44 showed decline in their QTc values during follow-up. The study also screened infants with WPW syndrome in 3, VPC in 9, CRBBB in 5, and situs inversus totalis in 1. Among 3 infants with WPW syndrome, 1 infant was diagnosed as noncompaction with heart failure (ejection fraction of 50% at the 1 st visit). A sharp drop of the ejection fraction to 28% emerged a few weeks later and medication was started. Conclusions: Electrocardiographic screening of one-month-old infants is successful in preventing deterioration of infants with risk and may prevent sudden infant death.
Adjuvant Bone-Targeted Therapies for Postmenopausal Breast Cancer
Authors: Caroline Wilson, Robert Coleman
Journal: JAMA Oncology (2016)

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Final results from PRIME: Randomized phase III study of panitumumab (pmab) with FOLFOX4 for first line metastatic colorectal cancer (mCRC).
Authors: J. Douillard, S. Siena, J. Cassidy, J. Tabernero, R. L. Burkes, M. E. Barugel, Y. Humblet, D. Cunningham, F. Xu, K. Krishnan
Journal: Journal of Clinical Oncology (2011)

3510^ Background: The primary analysis of PRIME demonstrated that pmab + FOLFOX4 significantly improved progression-free survival (PFS) vs FOLFOX4 for 1st line mCRC in patients (pts) with wild-type (WT) KRAS mCRC. Methods: Pts, randomized 1:1 to pmab 6.0 mg/kg every 2 weeks + FOLFOX4 (Arm 1) or FOLFOX4 (Arm 2), had no prior chemotherapy for mCRC, ECOG ≤2, and tumor tissue for biomarker testing. The primary endpoint was PFS by central assessment. Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. KRAS tumor status was determined by a blinded central lab prior to the primary analysis. This prespecified final descriptive analysis of PFS and OS was planned for 30 months (mos) after the last pt was enrolled. Results: 1,183 pts were randomized and received treatment (tx): 593 Arm 1, 590 Arm 2. 1,096/1,183 pts (93%) had KRAS results. Adverse event rates were consistent with the primary analysis. Results are shown (Table). Conclusions: In pts treated in Arm 1, PFS was improved, ORR was higher, and there was a trend toward improved OS in pts with WT KRAS mCRC, and PFS and OS were reduced in pts with mutant (MT) KRAS mCRC. OS was significantly affected by post study EGFR inhibitor use. KRAS testing is critical to select appropriate pts for tx with pmab. WT KRAS mCRC (n = 656) Arm 1 (n = 325) Arm 2 (n = 331) HR (95% CI) P valuea Median PFS - mos (95% CI) 10.0 (9.3 – 11.4) 8.6 (7.5 – 9.5) 0.80 (0.67 – 0.95) 0.009 Median OS - mos (95% CI) 23.9 (20.3 – 27.7) 19.7 (17.6 – 22.7) 0.88 (0.73 – 1.06) 0.17 ORRb - % (95% CI) 57 (51 – 63) 48 (42 – 53) Odds ratio (95% CI) 1.47 (1.07 – 2.04) 0.018 MT KRAS mCRC (n = 440) Arm 1 (n = 221) Arm 2 (n = 219) Median PFS - mos (95% CI) 7.4 (6.9 – 8.1) 9.2 (8.1 – 9.9) 1.27 (1.04 – 1.55) 0.02 Median OS - mos (95% CI) 15.5 (13.1 – 17.6) 19.2 (16.5 – 21.7) 1.17 (0.95 – 1.45) 0.15 ORRb - % (95% CI) 40 (33 – 47) 41 (34 – 48) Odds ratio (95% CI) 0.98 (0.65 – 1.47) 0.98 Pts receiving post-study anti-EGFR tx – n (%) Arm 1 Arm 2 WT KRAS 42 (12.9) 84 (25.4) MT KRAS 15 (6.8) 36 (16.4) Sensitivity analysis of OS using Branson-Whitehead approachc (pmab + FOLFOX: FOLFOX) WT KRAS 0.74 (0.61 – 0.90) 0.003 MT KRAS 1.06 (0.85 – 1.32) 0.6 a Descriptive. b Restricted to pts with baseline measurable disease per modified RECIST. c Stat Med 2002.
P31 Pattern and significance of biochemical abnormalities in referrals to a NAFLD clinic
Authors: G Masterton, P Hayes
Journal: Gut (2010)

Introduction  Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of referral to liver clinics, and accounts for around 11% of new patients. Despite this little is known of the typical pattern of liver biochemical abnormalities in this group. Many algorithms primarily use transaminases as their primary biochemical analyte. The aim of this project was to clarify common patterns and to determine their clinical significance.  Method  This was a single-centre, retrospective database study of all patients referred to a specialist NAFLD clinic between May 2006 and May 2009. Patients with any co-existing cause of liver disease, a history of excess alcohol or HOMA less than three were excluded from subsequent data analysis. For the 143 patients who remained a database search for contemporaneous blood results and clinical history was performed.  Results  Mean age at the time of referral was 55.8 years (SD 15.9). M/F=1:1.04. 54% were diabetic; 62% had hyperlipidaemia and 58% had a history of hypertension. 23 (16%) were deemed to be cirrhotic in the initial series of investigations. In this cohort elevated GGT was the commonest biochemical abnormality, present in 76.2% of referrals. GGT was elevated above 100 U/L in 38.5% of patients. In contrast, elevated ALT (>50U/L) was present in 58.0% of referrals; and was above 100U/L in 10.5%. Mixed ALT and GGT abnormalities were the commonest pattern of LFT abnormalities, present in 46.9%. A cholestatic pattern (here defined as an abnormal GGT but normal ALT) was present in 30.1% of referrals; elevated transaminases as an isolated abnormality were present in only 11.9% of referrals. On univariate analysis the only factors associated with elevated GGT was female gender (p=0.009) and the presence of cirrhosis (p=0.003). GGT >100 was associated with cirrhosis and increasing age on univariate analysis, however on multivariate analysis only the presence of cirrhosis remained statistically significant (p=0.005). Elevated ALT had no such association with cirrhosis and was negatively associated with the presence of diabetes and increasing age.  Conclusion  To date emphasis has been placed on serum transaminases in screening for NAFLD. However, in our cohort an elevated GGT was the commonest biochemical abnormality and, unlike transaminases, this was associated with the presence of cirrhosis. Biochemical profiles that omit GGT will be inadequate in screening for NAFLD.
Efficacy of targeted therapies after PD1/PD-L1 inhibitors in metastatic clear cell renal cell carcinoma (mRCC): A multi-institution retrospective cohort.
Authors: Laurence Albiges, Andre Poisl Fay, Wanling Xie, David F. McDermott, Daniel Yick Chin Heng, Charles Dariane, Guillermo De Velasco, Renee Elizabeth Lester, Bernard Escudier, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2015)

456 Background: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors showed activity in mRCC and are currently in development in first-line and previously treated patients (pts). Whether these drugs will modify efficacy of subsequent targeted therapy (TT) including VEGFR tyrosine kinase inhibitors (TKI) or mTOR inhibitors is unknown. Methods: Medical records of RCC patients treated with investigational PD-1 or PD-L1 inhibitors who received subsequent treatment with TT were reviewed in 4 institutions. Baseline characteristics at the time of subsequent therapy and outcome data including time to treatment failure (TTF), best response, 1 and 2 year overall survival (OS) were retrospectively collected. Results: Of 89 pts who received PD-1/PD-L1 inhibitors, 56 patients (M/F 39/17, clear-cell 53, IMDC good 3/intermediate 16/poor 11/unknown 26) have received a subsequent therapy after PD-1/PD-L1 blockade, while 7 patients are still on therapy and 26 patients did not receive subsequent therapy. Among these 26 patients, 12 died from disease and 14 are still alive off-systemic therapies. 43 pts received VEGFR TKI and 13 received mTOR inhibitors as first subsequent TT. Median follow up from start of the subsequent TT is 16.1 months (range: 0.2, 30.6 months). TT post PD-1/PD-L1 was administered as second line in 9 patients (16%), third line in 24 patients (43%), &gt; fourth line in 23 patients (41%). Median TTF was 6.9 months (range: 0.2+, 23.0), and was 6.9 and 5.7 months in patients who received VEGFR TKI and mTOR inhibitors respectively. One-year and 2-year OS from the initiation of subsequent TT was 58% (95% CI: 41-72%) and 36% (95% CI: 18%-54%), respectively. Investigator-assessed best response to subsequent TT was evaluated in 53 out of 56 patients: PR (n=7, 13%), SD (n=33, 62 %), and PD (n=13, 25%). Conclusions: This is the first report of TT efficacy after PD-1/PD-L1 inhibition. In this selected population, median TTF suggests a sustained benefit of both VEGFR TKI and mTOR inhibitors after PD-1/PDL1 inhibition.
Statistical Analysis of Operative Mortality and Recurrence in Intracranial Meningiomas
Authors: R. Assietti, G. Pinna, G. Introzzi, P. Gaetani, A. Tangenti, R. Rodriguez Y Baena, G. Sangiovanni, L. Magrassi, F. Rainoldi, G. Butti
Journal: Neuro-Oncology (1991)

A group of 23 clinical characteristics were tested with a stepwise logistic regression analysis to assess which group of factors best predicts the probability of survival of patients operated for intracranial meningioma. Ten clinical characteristics were tested with Kaplan-Meier curves and with Cox proportional hazard model to verify which best correlated with increased recurrence rate. Our results demonstrated that some multisystemic diseases like diabetes, hypertension, and some operative complications like hematoma were significantly related to an increased risk of operative mortality. The factors that heavily influenced the recurrence rate of meningiomas were the type of surgery and the histotype of the tumor.
Enoxaparin (E) and warfarin (W) differentially regulate tissue factor (TF), tissue factor pathway inhibitor (TFPI) and thrombin activatable fibrinolytic inhibitor (TAFI) in cancer patients with thrombosis
Authors: J. Fareed, D. Hoppensteadt, S. Cort, O. Iqbal, P. Bacher, D. Fareed, M. Tobu, S. Deitcher
Journal: Journal of Clinical Oncology (2005)

2057
The efficacy and safety of loading dose ibandronate in the treatment of non-small cell lung cancer metastatic bone pain(MBP)
Authors: S. Ren, L. Zhang, C. Zhou, S. Zhou, H. Sun
Journal: Journal of Clinical Oncology (2008)

19127 Background: Bone metastasis is a common complication in non-small cell lung cancer(NSCLC) and in which pain is the commonest presentation, besides conventional radiation and pain killers, bisphosphonates especially the third generation are indicated in MBP. We did this study to evaluate the efficacy and safety of initial loading dose Ibandronate in the treatment of NSCLC metastatic bone pain. Methods: 48 cases of NSCLC patients with MBP were errolled into this study from May 2006 to Oct 2007, received loading dose Ibandronate, initially 6 mg administered intravenously on 3 consecutive days for about 15 minutes, then 6 mg maintained once a time per 3–4 weeks. Pain scores and QOL scores were accessed on the first 7 days and after 3–4 weeks by numeric rating scale and LCSS respectively, daily morphine consumption doses were recorded, also the serum markers such as calcium, creatinine, alkaline phosphatase and urine protein were monitored. Results: 47 cases were eligible to evaluate the efficacy and safety, including 29 males and 18 females with the midian ages of 55 years old. 40 cases (85.1%)were effective and the average initial response time was 3.0±0.7 days; There were a significant decrease both in pain scores(5.5±1.8 VS 2.9±2.7 P<0.001)and QOL scores (11.2±3.8 VS 5.9±4.7 P<0.001) after receiving the loading dose therapy. 8 patients reduced morphine consumption amount for about 20–60mg and the serum calcium of 11 hypercalcemia patients decreased to normal range after the treatment. Side effects were mild and acceptable, including 10 cases of mild fever who recovered without any additional treatment and 2 cases of muscular spasms who recovered after calcium supplementation, no renal toxicity and osteonecrosis of the jaw happened. Conclusions: Loading dose, consecutive three day administration of ibandronate took effects quickly with mild side effects, it could relive metastasis bone pain and improve QOL significantly, reduced the morphine consumption and will be a new promising option to treat the MBP of NSCLC. No significant financial relationships to disclose.