tbuckley/cabot-search huggingface dataset:
Defining significant adverse events (AEs) in advanced colorectal cancer (Adv CRC) patients in the community oncology practice setting
Authors: P. G. Kwan, J. M. Koeller, J. Simon, T. McKibbin
Journal: Journal of Clinical Oncology (2006)

6017 Background: In contrast to clinical trials, standard (ie WHO) AE criteria are rarely used in community practice (CP). Because focusing on clinical decisions has more utility, we define a clinically significant (sig) AE as one resulting in deviation from planned chemo delivery. AEs are broadly categorized as tox resulting in a regimen change, a dose decrease, a delay, or an extra visit/hospitalization. Methods: Retrospective study. From 7/05–12/05 a team of oncology RPhs went on-site to 4 large US clinics (OH, NV, ME, FL), capturing all available Adv CRC pts receiving chemo. Pt, regimen, line of therapy, drug, cycle (cy), treatment (tx), toxicity (tox), and delay information were recorded. Delays were categorized as admin/other delays or tox-related delays. Pts who expired before 1/1/03 were excluded. Results: 207 pts (74 expired) received 2,444 cycles (79% from ‘04–05) Avg age = 65 years, 50% male and median ECOG PS = 1. Median survival = 17 mo. Six hundred two sig AEs (24.6% of cycles, combined endpt) were recorded (see Table ). The top regimens (cycles) were: 1st line - Folfox4 (427), IFL (259), Roswell Park (157), CapeOX (89), Folfox 6 (76), Cape Single Agent (73), Folfiri2 (62); 2nd line - Folfox4 (115), CPT11 Single Agent (96), CapeOX (71), IFL (60), Cape Single Agent (57), Roswell Pk (53), Folfiri2 (47). MoAb (cetuximab/bevacizumab) was added in 48% of regimen cycles. Of interest, single agent cpt11 (+MoAb in 80% of cy) is a common 2nd-line regimen. Two other references describe this regimen (Saltz Proc ASCO 2001; Cunningham NEJM 2004). Our data confirm this regimen’s tolerability. Conclusion: In the tx of Adv CRC, there is a wide variation in community oncologist prescribing patterns. We defined regimen tox based on criteria focusing on clinical decision making and showed the feasibility of measuring tox-related delays apart from other non-tox delays. Toxicity reported in this fashion may prove valuable for oncology administrators seeking to employ disease management strategies. [Table: see text] [Table: see text]
Familial Catecholamine-Induced QT Prolongation in Unexplained Sudden Cardiac Death
Authors: Francois Huchet, Florence Kyndt, Julien Barc, Aurelie Thollet, Flavien Charpentier, Richard Redon, Jean Jacques Schott, Herve Le Marec, Vincent Probst, Jean-Baptiste Gourraud
Journal: Journal of the American College of Cardiology (2017)
Familial melanoma in Spain: Preliminary report of the FAM-GEM-1 study.
Authors: Manuel Martin-Gonzalez, Pablo Cerezuela, Alfonso Martin-Carnicero, Teresa Puertolas, Salvador Martin-Algarra, Irene Gil-Arnaiz, Cayetana Maldonado-Seral, Maria Gonzalez Cao, Joaquin Belon, Jose Antonio Aviles Izquierdo, Ivan Marquez-Rodas
Journal: Journal of Clinical Oncology (2013)

e20015 Background: In addition to environmental factors and phenotype, melanoma risk is determined by familial background. It is estimated that 5-10% of melanoma cases occur in a familial setting. High susceptibility genes like CDKN2A and intermediate risk like M1CR are the most known, but explain less than 1/3 of the cases, most of them cases with 2 or more first degree relatives involved, the classical definition for familial melanoma (FM). In Spain there are several local studies about epidemiology and characteristics of FM, but there are no studies that cover all the territory. Methods: FAM-GEM-1 is a national, observational, 2 years-registry study (2011-2013), conducted by the Spanish Multidisciplinary Melanoma Group (GEM), whose principal objective is to assess the rate of melanoma patients with family history of melanoma in Spain. Secondary objectives are to analyze whether patients with family history are different from sporadic melanoma in terms of clinical, pathological and molecular features; and to constitute a registry of FM in order to deeper characterise these patients in further studies. We present the exploratory results of the first 219 patients registered Results: See Table. Conclusions: We have found that almost 9% of patients have family history of melanoma. Of them, almost 3/4 fulfils familial melanoma criteria. It seems that there are not relevant differences among sporadic and familial melanoma in our registry, except for sex, although the preliminary nature of the results makes necessary more patients in order to determine if there are clinical and/or pathological differences between both groups. [Table: see text]
ABCB1 polymorphism as a prognostic factor in breast cancer patients with neoadjuvant chemotherapy.
Authors: Hee Jun Kim, Seock-Ah Im, Hye Seon Ham, Kyung Hun Lee, Tae Yong Kim, Yu Jeong Kim, Do-Youn Oh, Jee Hyun Kim, Wonshik Han, In-Jin Jang, Tae-You Kim, In Ae Park, Dong Young Noh
Journal: Journal of Clinical Oncology (2014)

1038 Background: Expression of the adenosine triphosphate-binding cassette B1(ABCB1) transporter and P-glycoprotein are associated with resistance to anticancer drugs. The purpose of this thesis was to investigate the role of single nucleotide polymorphism (SNP) in the ABCB1 and CYP3A genes in breast cancer patients who were treated with neoadjuvant docetaxel and doxorubicin chemotherapy. Methods: Stage II or III breast cancer patients were treated with 3 cycles of neoadjuvant, after which the patients received curative surgery and adjuvant chemotherapy with the same regimen. The polymorphisms of ABCB1 (C3435T, G2677T/A, and C1236T) and CYP3A were genotyped. The correlation of genetic polymorphisms of ABCB1, CYP3A, and clinical outcomes was analyzed. Results: Among the 216 patients, ABCB1 3435TT genotype had a longer OS than CT/TT. With univariate analysis, good PS, invasive ductal carcinoma, initial operable stage, ER-positivity, non-triple negative phenotype, breast conserving surgery and the TT genotype of C3435T were associated with a lower risk of death. Multivariate analyses demonstrated that good PS, invasive ductal carcinoma, non-triple negative phenotype and initial operable stage were significantly associated with the OS. ABCB1 3435TT genotype had a higher AUC than CC/CT genotype for docetaxel (p=0.031). These higher AUCs in the C3435TT genotype was associated with increased toxicities of neutropenia (p=0.037) and diarrhea (p=0.017). Conclusions: This study showed that the genetic polymorphism of ABCB1 C3435T might be associated with a longer OS. Our results also suggest that the prediction of docetaxel toxicity might be possible for C3435T polymorphism. Larger prospective studies as well as functional studies in human subjects are warranted.
First-line dacomitinib (PF-00299804), an irreversible pan-HER tyrosine kinase inhibitor, for patients with <i>EGFR</i>-mutant lung cancers.
Authors: Mark G. Kris, Tony Mok, Sai-Hong Ignatius Ou, Renato Martins, Dong-Wan Kim, Zelanna Goldberg, Hui Zhang, Ian Taylor, Stephen P. Letrent, Pasi Antero Janne
Journal: Journal of Clinical Oncology (2012)

7530 Background: Dacomitinib irreversibly inhibits EGFR, HER2 and HER4, and showed superior activity vs. reversible EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer models, including resistant forms. This open-label Phase II study evaluates dacomitinib as 1st-line treatment (tx) for patients (pts) with lung cancers. Pts with sensitizing EGFR deletions/mutations in exons 19 or 21 are reported here. Methods: Pts had stage IIIB/IV adenocarcinoma, no prior systemic tx, had smoked &lt;10 pack years (none within 15 years of enrollment) or had known EGFR mutation. Pts received dacomitinib orally once daily continuously at 45 mg, or 30 mg with the option to escalate to 45 mg; evaluation was every 28 days. Endpoints included progression-free survival rate at 4 months (PFS at 4M, primary); PFS, and partial response (PR) rate. Results: 92 pts enrolled; 47 had EGFR mutation in exons 19 (n=25) or 21 (n=22), 33 were female and 27 Asian. 34/46 evaluable pts with EGFR exon 19 or 21 mutations had a PR (PR rate = 74%; 95% CI: 59–86; exon 19 = 72%; exon 21 = 76%). PR rates and preliminary PFS were not significantly different for exons 19 and 21. Preliminary PFS at 4M was 96% (95% CI: 84–99), preliminary PFS rate at 1 year was 77% (95% CI: 61–87) and preliminary median PFS was 17 months (95% CI: 13–24). Median tx duration was 13.1 months. For pts with EGFR wild-type lung cancers, PR and PFS at 4M rates were 7% (n=14; 95% CI: 0–34) and 33% (n=14; 95% CI: 11–58), respectively, and for pts with EGFR unknown lung cancers, 46% (n=22; 95% CI: 24–68) and 68% (n=24; 95% CI: 45– 83), respectively. 7 pts had lung cancers with non-sensitizing EGFR mutations; 2 had a PR and 3 SD. For all 92 pts, common side effects included dermatitis acneiform (grade 3/4 = 17%/0) and diarrhea (14%/0). 3/46 pts with EGFR exon 19 or 21 mutations discontinued tx due to drug-related toxicity. Conclusions: 74% of pts in this cohort with EGFR exon 19 or 21 mutant lung cancers experienced PRs with 1 st -line dacomitinib; preliminary PFS rate was 77% at 1 year; preliminary median PFS was 17 months; further research is planned in this pt population. As dacomitinib is well tolerated, with preclinical activity against HER2, a cohort of pts with HER2 mutant lung cancers is recruiting.
Predictive factors of contralateral paratracheal lymph node metastasis in unilateral papillary thyroid carcinoma.
Authors: Tao Wei, Rui Chen, Xiuhe Zou, Feng Liu, Zhihui Li, Jingqiang Zhu
Journal: Journal of Clinical Oncology (2015)

e17005 Background: Most of unilateral papillary thyroid carcinoma (PTC) metastasize to ipsilateralparatracheal lymph nodes(LNs) while some had contralateral paratracheal LN involved. The aim of this study was to analyze the predictive factors of contralateral paratracheal LN metastasis in unilateral PTC. Methods: Data on 332 patients with unilateral PTC who underwent total/near total thyroidectomy and bilateral central neck dissection (CND) with/without lateral neck dissection were collected retrospectively. Patients’ demographics, the extent of surgeries, and the pathological status of LNs and primary tumor were analyzed. Results: A total of 332 patients (67 male and 265 female) were included. Contralateral paratracheal LN metastasis was found in 68 (68/332, 20.5%) patients. Tumor size (＞ 1 cm) (P < .001), capsular/extracapsular invasion (P < .001), pretracheal/prelaryngeal LN metastasis (P < .001), lateral neck LN metastasis (P < .001) and ipsilateral/paratracheal LN metastasis (P < .001) was significantly associated with contralateral paratracheal LN metastasisonunivariate analysis. Multivariate analysis showed that tumor size (> 1 cm)(P = 0.013), capsular/extracapsular invasion (P = 0.009), pretracheal/prelaryngeal LN metastasis (P=0.021) and lateral neck LN metastasis (P = 0.002) were independent risk factors of contralateral paratracheal LN metastasis. Conclusions: Primary tumor size ＞ 1 cm, capsular/extracapsular invasion, pretracheal/prelaryngeal LN metastasis andlateral neck LN metastasis are predictive factors of contralateral paratracheal LN metastasis in unilateral PTC, which may help to determine the optimal extent of CND in patients with PTC.
Association of Dermatology Consultations With Patient Care Outcomes in Hospitalized Patients With Inflammatory Skin Diseases
Authors: Nima Milani-Nejad, Myron Zhang, Benjamin H. Kaffenberger
Journal: JAMA Dermatology (2017)

The value of inpatient dermatology consultations has traditionally been demonstrated with frequency in changes of diagnosis and management; however, the impact of dermatology consultations on metrics such as hospital length of stay and readmission rates remains unknown.To determine the association of dermatology consultations with patient care in hospitalized patients using objective values.We retrospectively queried the deidentified database of patients hospitalized between January 1, 2012, and December 31, 2014, at a single university medical center. A total of 413 patients with a primary inflammatory skin condition discharge diagnosis and 647 patients with primary inflammatory skin condition admission diagnosis were selected.Hospital length of stay and 1-year readmission with inflammatory skin conditions.The 413 patients with a primary inflammatory skin condition discharge diagnosis were 61.0% female and had a mean (SD) age of 55.1 (16.4) years. The 647 patients with primary inflammatory skin condition admission diagnosis were 50.8% female and had a mean (SD) age of 57.8 (15.9) years. Multivariable modeling showed that dermatology consultations were associated with a reduction of 1-year inflammatory skin condition readmissions among patients who were discharged primarily with an inflammatory skin condition (readmission probability, 0.0025; 95% CI, 0.00020-0.030 with dermatology consult vs 0.026; 95% CI, 0.0065-0.10 without; odds ratio, 0.093; 95% CI, 0.010-0.840; P = .03). No other confounding variable was associated with reduction in readmissions. Multivariable modeling also showed that dermatology consultations were associated with a reduction in the adjusted hospital length of stay by 2.64 days (95% CI, 1.75-3.53 days; P < .001).Dermatology consultations were associated with improvements of outcomes among hospitalized patients. The expansion of the role of dermatology consultation services may improve patient care in a cost-effective manner.
Clinical impact of loss of H3K36me3 expression in patients with clear cell renal cell carcinoma.
Authors: Abhisek Swaika, Thai Huu Ho, Payal Kapur, Daniel Serie, Jeanette Eckel-Passow, James Brugarolas, Alexander S. Parker, Richard Wayne Joseph
Journal: Journal of Clinical Oncology (2015)

4563 Background: Mutations in chromatin modifying enzymes play a role in the pathogenesis of clear cell renal cell carcinoma (ccRCC). However the clinical impact of histone methylation regulated by chromatin modifying enzymes remains unknown. Herein we analyze the clinical impact of loss of histone H3 lysine 36 trimethylation (H3K36me3) in a large cohort of ccRCC tumors and associate its expression with renal cell cancer-specific survival (RCC-SS) and pathologic features. Methods: We utilized the Mayo Clinic Renal Registry and identified 1454 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/3/1990 and 4/14/2009 and who also had available tissue samples. We used immunohistochemistry (IHC) to detect H3K36me3 expression, and a central pathologist blinded to the outcomes scored tumors as either positive or negative. Tumors with heterogeneous or equivocal staining were not included in this analysis. For associations with pathologic features we employed Mann-Whitney U tests, and for associations with relapse free survival (RFS) and ccRCC-SS we generated Cox proportional hazard regression models. Results: Of the total 1454 samples, 1205 (83%) were scored as either positive or negative for H3K36me3 with 978 (81%) positive and 227 (19%) negative samples. H3K36me3 negative tumors strongly associated with male gender, older age, larger tumor size, higher grade (3-4), and positive tumor necrosis (p < 0.001 for all). After adjusting for age, H3K36me3 negative patients had decreased RFS (HR 2.87, p < 0.001) and decreased RCC-SS (HR 3.10, p < 0.001). After adjusting for age and the Mayo Clinic-Stage, Size, Grade, and Necrosis (SSIGN) score, H3K36me3 negative tumors continued to have decreased RFS (HR 1.30, p = 0.041) and trended towards decreased RCC-SS (HR 1.31, p = 0.064). Conclusions: This is the largest study evaluating the clinical significance of H3K36me3 expression in patients with ccRCC. Loss of H3K36me3 is a marker of poor prognosis and an independent predictor of decreased RFS. Efforts to elucidate the mechanisms of how loss of H3K36me3 contributes to worse tumor biology are underway.
Hepatitis B reactivation in HBsAg-/cAb+ patients receiving rituximab: A meta-analysis.
Authors: Lee Mozessohn, Kelvin K. Chan, Jordan J. Feld, Lisa K Hicks
Journal: Journal of Clinical Oncology (2013)

6592 Background: Patients with hepatitis B virus (HBV) who are HBsAg+ are recognized to be at risk of HBV reactivation if rituximab is administered in the absence of antiviral treatment. Recently, it has been reported that patients with so-called “resolved HBV infection”(HBsAg-/cAb+) may also be at risk; however, the degree of risk is not known. Methods: We performed a systematic review of the English and Chinese language literature in Medline (1996 to July week 2 2012) and Embase (1996 to 2012 week 29) using the MeSH terms “lymphoma” and “hepatitis B”. Eligible studies were limited to those reporting primary data on HBV reactivation rates in HBsAg-/cAb+ patients receiving rituximab. We excluded case series with less than 5 patients. Pooled estimates were calculated for HBV reactivation and the impact of HBsAb status on HBV reactivation rate was explored. Results: Data from 445 patients in 12 studies were included. Using a standardized definition of HBV reactivation, (ALT &gt;3 x upper limit of normal AND either an increase in HBV DNA from baseline OR HBsAg seroreversion), the pooled estimate for the risk of HBV reactivation in HBsAg-/cAb+ patients was 5.4% (I 2 = 63%, P = 0.009). Significant heterogeneity was apparent. Exploratory analyses suggested that patients were less likely to reactivate if they were HBsAb+ (OR = 0.32; 95% CI 0.12-0.85, P = 0.0285). Conclusions: Our meta-analysis confirms that there is a measurable risk of HBV reactivation in HBsAg-/cAb+ patients exposed to rituximab HBsAb+ patients may be at lower risk than those who are HBsAb-. However, heterogeneity in the risk estimates limits their generalizability. Large prospective studies are needed to clarify the risk of HBV reactivation in HBsAg-/cAb+ patients and to inform decisions about best practice.
Systematic determination of EGFR mutation (m) and immunohistochemistry (IHC) of ALK translocation (t) status in patients (p) with newly non-small cell lung cancer (NSCLC).
Authors: Santiago Ponce Aix, Jon Zugazagoitia, Pilar Isabel Gonzalez Marquez, Maria Angeles Torres Nieto, Joan Magasent Blesa, Xabier Mielgo, Carmen Gonzalez Paz, Rosa Quiben, Juan Luis García Llano, Carmen Perez Agua, Pilar Resano, Julia Calzas, Lourdes Garcia, Victor M. Diaz Muñoz, Lara Iglesias, Juan A. Núñez, Rosa M. Garcia Martin, Hernan Cortes-Funes, Jose Luis Rodriguez Peralto, Ana Belen Enguita Valls
Journal: Journal of Clinical Oncology (2014)

e22112 Background: Detection of EGFR m in p with NSCLC is done in a routine way. Given the data published on ALK positive p detection is crucial for therapeutic decision making. ALK t should be performed using FISH break apart probes for selecting p but probably is not enough quick for clinical wide use. Based on promising results IHC assay may be used as screening. We implemented a systematic determination of EGFR m and ALK t status to asses feasibility and accuracy in a clinical setting. Methods: We have tested all p with newly diagnosed NSCLC (non squamous or squamous with a light smoking history) from 12 centers. All samples were send to H. 12 de Octubre (June -December 2013). The objective was to evaluate the accuracy of EGFR m testing (TheraScreen/Cobas test) and ALK t testing. We performed IHC, as screening, using Ventana D5F3 mouse monoclonal antibody. P with positive IHC were checked using Abbot Vysis Break Apart. Results: 366 p were tested for EGFR/ALK simultaneously. 109 (29.78 %) were women and 257 (70.21 %) men. 361 (98.63 %) caucasian and 5 (1.36 %) asiatics. 246 (67.21 %) adenocarcinoma, 60 (16.39 %) non other specify, 35 (9.56 %) squamous, 17 (4.64 %) large cell carcinoma, 6 (1.63 %) adenosquamous and 2 (0.54 %) large cell carcinoma with neuroendocrine differentiation. 125 (34.15%) former smokers, 100 (27.32 %) current smokers, 97 (26.5 %) unknown and 44 (12.02 %) never smokers. The tumor sample was paraffin embedded (89.61 %) and cytology (10.38 %). We performed successfully EGFR test in 97.27 % and IHC in 95.91 %. The median time to results was 5.8 days. 29 p with EGFR m (7.92) were found: del 19 (58.62%) 21 L858R (20.68%) exon 18 (6.88%) 20 ins (10.34%) and one double mutation (18-G719X plus 20-S7681).15 p with IHC ALK t positive (4.09%) were found; all of them were confirmed by FISH with full concordance. Most of the ALK t patients were adenocarcinoma (86.66%) but 1 adenosquamous and 1 squamous. Conclusions: Systematic determination of EGFR m. and ALK t. in several public centers is feasible offering a good time to result and good performance. In our experience IHC should be done, instead FISH, in all non squamous NSCLC patients and in those squamous with light smoking history.
Phase I study of vandetanib (ZD6474) administered during and after irradiation (RT) in children with diffuse intrinsic pontine glioma (DIPG)
Authors: A. Broniscer, T. E. Merchant, C. Hillenbrand, Z. Patay, T. K. Chin, A. Onar, S. C. Kaste, R. J. Gilbertson, A. Gajjar
Journal: Journal of Clinical Oncology (2009)

10020 Background: Children with DIPG have a dismal prognosis despite use of RT, which is the mainstay of therapy. All chemotherapy regimens used so far demonstrated no benefit. EGFR and VEGFR pathways are considered important in tumorigenesis of DIPG. Methods: We conducted a traditional phase I study combining oral vandetanib (VEGFR-2 and EGFR inhibitor) during and after local RT in children with DIPG. Five dosage levels were tested (50, 65, 85, 110, and 145mg/m 2 per day). Vandetanib and RT started on the same day. The first 6 weeks of therapy constituted the dose-limiting toxicity (DLT)-evaluation period. Correlative studies consisted of pharmacokinetic analysis (PK), pharmacodynamic studies in blood, and standard and investigational imaging (before and 1, 3, and 6 weeks after start of therapy). Results: Twenty-one patients were enrolled on study (50 [n = 3], 65 [n = 3], 85 [n = 3], 110 [n = 6], and 145mg/m 2 [n = 6]). Two patients experienced DLT consisting of rash/mucositis (level 4) and diarrhea (level 5). The maximum-tolerated dose (MTD) of vandetanib was not reached. Other significant toxicities included lymphopenia grade 3/4 (n = 10), grade 3 neutropenia and hypophosphatemia (one each), grade 2 proteinuria (n = 2), grade 2 hypertension (n = 4), and mild QTc prolongation (n = 7) .Once the phase I component was completed, two extra patients were enrolled at dosage level 5; one of them developed grade 4 seizure secondary to posterior reversible encephalopathy syndrome. PK (n = 21) showed similar drug clearance and volume of distribution compared to adults. However, drug exposure at steady state normalized by dose seemed higher in children. Increased tumor perfusion during the first 6 weeks of therapy was observed in the first 12 patients analyzed. Conclusions: Although MTD was not reached, we recommend administration of vandetanib at a dose of 110mg/m 2 per day during and after local RT in children. Further combination studies of vandetanib in children with DIPG are planned. No significant financial relationships to disclose.