tbuckley/cabot-search huggingface dataset:
Rates of trastuzumab-associated cardiotoxicity in patients with HER2-positive breast cancer at a tertiary cancer centre.
Authors: Nidhi Kumar Tyagi, Roochi Arora, Arun Partridge, Mithula Tharmabala, Som Mukherjee, Darryl Leong, Sukhbinder K. Dhesy-Thind
Journal: Journal of Clinical Oncology (2017)

e12030 Background: Human epidermal growth factor receptor 2 ( HER2) is overexpressed in 15-25% of breast cancers and associated with decreased rates of survival. Trastuzumab (TZ) is a humanized monoclonal antibody that binds against HER-2 and improves both disease free and overall survival in the adjuvant setting. A side effect of TZ is reversible cardiotoxicity(CT), which can lead to early termination of TZ. The rates of TZ associated CT seen in trials range between 1-16%. These rates may not be representative of clinical practice. Our aim is to identify the rate of TZ-associated CT and the rate of early discontinuation of TZ associated CT at the Juravinski Cancer Centre (JCC), in Hamilton, Ontario. Methods: Patients treated with adjuvant TZ between 2006-2013 at JCC were identified using JCC pharmacy data and included in this audit. We examined patient charts for relevant clinical-pathologic variables, cardiac Results: Results are shown in the table below. Conclusions: In conclusion, we found that rates of CT were higher at JCC than in clinical trials. This is not unexpected as patients with known cardiac risk factors and history of cardiac disease were excluded from most clinical trials. Strategies to optimize cardiac risk factors and management of CT are needed. We have opened a cardio-oncology clinic at JCC and initiated a clinical trial examining the feasibility of ongoing TZ therapy in the setting of mild DLVEF. [Table: see text]
Fat depletion in liver transplant candidates with autoimmune hepatitis as compared to alcohol-related liver disease
Authors: A Qasim, O O'Conor, J Sultan, D Brady, J Hegarty, A McCormick
Journal: Endoscopy (2006)

Patients and methods: Patients assessed for liver transplantation from June 2003 to March 2005 were included. Patient characteristics, underlying liver disease, body weight and height were recorded. Anthropometric measurements included triceps skin fold (TSF) thickness, mid arm circumference (MAC) and mid arm muscle circumference (MAMC).
Abstract #3715: The inhibition of ABL kinase activity by nilotinib and imatinib, but not dasatinib, is time-dependent
Authors: Paul Manley, Sandra Cowan-Jacob, Gabriele Fendrich, Janis Liebetanz, Jürgen Mestan, Nicole Martin, Doriano Fabbro
Journal: Cancer Research (2009)

Nilotinib is a highly potent, selective BCR-ABL kinase inhibitor with significant clinical efficacy in the treatment of patients with chronic myeloid leukemia in chronic or accelerated phase, who have failed prior therapy including imatinib. The molecular basis for this activity stems from binding to the ABL kinase domain in a conformation (DFG-out) where the activation-loop is folded into the unphosphorylated ATP-binding pocket, thereby blocking access by ATP. Kinase inhibition resulting from this mechanism can be readily quantified in cellular assays through either direct effects on full-length BCR-ABL autophosphoylation (IC50) or on BCR-ABL dependent cell proliferation (GI50). Thus in BCR-ABL transfected Ba/F3 cells and the K562 CML cell line, nilotinib displays IC50 values of 20±2 & 43±15 nM and GI50 values of 25±1 & 12±2 nM respectively. We postulated that in biochemical assays this mechanism of action might lead to time-dependent ABL inhibition, due to the need for the enzyme to adopt the DFG-out conformation, as reported for other kinase inhibitors, such as BIRB796 bound to MAPK and lapatinib bound to EGFR. Here we report the time-dependent inhibition of ABL by nilotinib and imatinib. ABL1A (64-515; SH2, SH3 and catalytic domain) was preincubated at 22oC with drug prior to assessment of catalytic transphosphorylation activity (substrate: Poly[Ala6Glu2LysHBr5Tyr1]) in the presence of 20 \#956;M ATP (0.1 \#956;Ci [\#947;-33P]-ATP) using the filter-binding technique (15 min incubation).$$table_{E24F6FFF-55B7-49C8-A777-FDEBF9DFAD85}$$ Imatinib and nilotinib displayed time-dependent ABL inhibition, to give similar equilibrium IC50 values; at 4oC nilotinib required 180 min to reach an IC50 of 46 nM. The time-dependency of nilotinib probably reflects a slow off-rate of binding, which is predictive for high in vivo selectivity and might be an important component of this drug\#8217;s efficacy in CML. Dasatinib showed no time-dependency, consistent with it binding the phosphorylated DFG-in active conformation of ABL (J Biol Chem 2008;283:18292).  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3715.
Phase II randomized trial of irinotecan/temozolomide (I/T) with temsirolimus (TEM) or dinutuximab plus granulocyte colony stimulating factor (DIN/GMCSF) in children with refractory or relapsed neuroblastoma: A report from the Children’s Oncology Group (COG).
Authors: Rajen Mody, Arlene Naranjo, Collin Van Ryn, Alice L. Yu, Wendy B. London, Barry L. Shulkin, Marguerite T Parisi, Sabah-E-Noor Servaes, Mitchell B Dicciani, Paul M. Sondel, John M. Maris, Julie R. Park, Rochelle Bagatell
Journal: Journal of Clinical Oncology (2016)

10502 Background: Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of I/T has activity in patients with relapsed disease, and the toxicity profile of I/T makes it an excellent backbone for study of new agents. Temsirolimus (TEM) and dinutuximab (DIN) were selected for testing in combination with I/T in subjects with relapsed, progressive or refractory neuroblastoma. Methods: COG ANBL1221, a randomized Phase II selection design trial, compared response and toxicity in subjects treated with I/T in combination with either TEM (Arm A) or DIN/GM-CSF (Arm B). Patients were eligible at first relapse/progression or first designation of primary refractory disease. Randomization was stratified based on prior therapy and MYCNstatus. Cycles were administered every 21 days. Partial and complete responses (PR, CR) were confirmed centrally. Results: Thirty-five eligible patients were enrolled. Median age was 5.7 years (range 2.1-16.2), 24 pts had measurable disease (12 per arm). The 18 subjects randomized to Arm A received 89 total courses (median 3); 1 PR was observed (5%). The 17 patients randomized to Arm B received 136 total courses (median 6). Nine (53%) had objective responses (4 PR, 5 CR), including responses in 5 of 10 patients with relapsed/progressive disease and 4 of 7 with refractory disease. Among Arm B responders, prior therapy included high dose chemotherapy with stem cell rescue in 5 and anti-GD2 therapy in 3. One patient with rapidly progressive thoracic disease experienced Grade 4 hypoxia during Arm B therapy; no other subject experienced unanticipated toxicity. Arm B met protocol-defined criteria for selection as the optimal combination for further study. Conclusion: I/T/DIN/GM-CSF shows significant anti-tumor activity in patients with relapsed/progressive or refractory neuroblastoma. Additional study of this combination will include evaluation of clinical and biological markers that may identify patients most likely to respond to this active chemo-immunotherapeutic regimen. Clinical trial information: NCT01767194.
Neoadjuvant carboplatin and docetaxel in locally advanced triple negative breast cancer: A Hispanic trial.
Authors: Saul Campos Gomez, Karen Angelica Campos Gomez, Marciela Garcia Garces, Gladys Morelos, Jesus Hernandez Alvarez
Journal: Journal of Clinical Oncology (2016)

e12554 Background: To evaluate the impact on efficacy and safety of combination of carboplatin plus docetaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC in a Hispanic Cohort. The primary endpoint of the study was pathologic complete response (pCR), with secondary endpoints including clinical response and safety of the combination. Methods: Patients with biopsy confirmed pathological diagnosis of locally advanced invasive breast cancer, triple negative by immunohistochemistry, and with indication for NACT were eligible in this study. A total of thirty five patients (n = 35 ) were enrolled from January 2013 to November 2015 with stage II to III TNBC. Received doxorubicin plus cyclophosphamide once every 3 weeks for four cycles followed by docetaxel 75 mg/m(2) every three weeks for 4 cycles with concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results: Overall, 35 patients were enrolled from January 2013 to August 2015. 33 patients completed chemotherapy as planed while one patient discontinued platinum due to ototoxicity. pCR rate was 50%. All the 35 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (70 %), nausea (40 %) and vomiting (30%). Grade 3/4 toxicities were low. Ninety four per cent of patients completed six cycles. Conclusions: In locally advanced TNBC, addition of carboplatin to docetaxel regimen in NACT notable increased pCR rates compared with the standard anthracycline plus paclitaxel regimen reported in the literature. This regimen is highly effective, well tolerable and feasible in TNBC.
Translating Patient-Reported Outcomes From Surgical Research to Clinical Care
Authors: Angela B. Smith, Margaret L. Schwarze
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Traumatic Aneurysms of the Thoracic Aorta
Authors: Joseph J. Garamella, W. Robert Schmidt, Nathan K. Jensen, Michael F. Lynch
Journal: New England Journal of Medicine (1962)

FOUR cases of traumatic aneurysm of the thoracic aorta due to nonpenetrating trauma have been surgically treated by us. One of these patients was operated upon ten days after spontaneous rupture of the aneurysm into the esophagus. Rupture of a traumatic aneurysm over a few months' duration has not previously been reported,1 and this case is therefore presented in detail. Certain clinical and operative features of these cases are summarized in Tables 1 and 2.Case ReportsCase 1. S.O.P., a 38-year-old farmer, was admitted to the hospital on July 7, 1955, with the complaint of chest pain between the shoulder blades, . . .
Colorectal peritoneal carcinomatosis treated by completed surgery plus systemic chemotherapy: Futility of HIPEC?
Authors: Gregoire Desolneux, Camille Maziere, Marianne Fonck, Dominique Bechade, Yves Becouarn, Jeremy Vara, Veronique Brouste, Caroline Lalet, Serge Evrard
Journal: Journal of Clinical Oncology (2014)

e14513 Background: Cytoreductive peritoneal surgery (CPS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC) is considered as the standard treatment for colorectal peritoneal carcinomatosis (CPC). Complete CPS efficacy has been demonstrated but evidence supporting HIPEC’s role is lacking. Methods: We report our experience for surgical treatment of CPC without adjunction of HIPEC. From 2003 to 2013, all patients who underwent a CPS for CPC were retrospectively identified. Overall survival (OS), progression-free survival (PFS) and outcomes were recorded. Statistical analysis was performed using SPSS software. Kaplan-Meier survival estimates were calculated. Results: There were 53 patients with CPS out of 103 patients with CPC that were identified, 25 males and 28 females with a mean age of 60.2. There were 25 patients (52.8%) who had other site of metastases mostly liver (20) and lung (7). For 26 patients (49.1%) carcinomatosis was synchronous. There were 18 (34%) patients who underwent pre-operative chemotherapy, 35 (66%) post-operative chemotherapy, and among them, six had pre- and post-operative. Median Peritoneal Carinomatosis Index (PCI) was 9 (1-25). Median follow-up was 52.3 months. There were 28 patients (52.8%) alive, 13 without cancer, 15 with. Of 25 deaths, 23 died from the cancer. Median survival was 46.1 months. OS at one, three, and five years were respectively 94%, 61.67%, and 40.12%. PFS at one and three years were respectively 72.91% and 4.68%. In univariate analysis, presence of extraperitoneal metastases was significantly (p=0.013) associated with a poor survival with median survival of 30.7 months compared to patients without extraperitoneal disease who had a median survival of 75.2 months. There were 43 patients who had a recurrence (35 CPC, 30 other metastases, and two local recurrence). Mean progression time was 14.9 months. In univariate analysis PCI> = 10 was correlated with poor PFS (p=0.03). There were 24 (45.3%) patients who underwent post-operative complications, 14 (26.4%) medical complications, 19(35.8%) surgical, and nine both. Conclusions: Compared to the results in the literature after CPS for CPC + HIPEC, our survival results are similar with less complication. The benefit of HIPEC remains hypothetical.
Routine tumor next-generation sequencing (NGS) to identify rare germline lung cancer risk mutations in EGFR and ERBB2.
Authors: Ruthia Chen, Diane R. Koeller, Lynette M. Sholl, Michael S. Rabin, Matthew B. Yurgelun, Anu B. Chittenden, Judy Ellen Garber, Geoffrey R. Oxnard
Journal: Journal of Clinical Oncology (2017)

1513 Background: New insights into lung cancer genomics has required a new look at genetic determinants of inherited lung cancer risk. There are now four germline mutations in lung cancer oncogenes (EGFR T790M, V843I, R776H; and ERBB2 G660D) which have been reported in kindreds with a high prevalence of lung cancer in nonsmokers. We hypothesized that routine tumor NGS could be used to find rare kindreds with inherited lung cancer risk. Methods: An institute-wide database of tumor NGS results was queried for cases positive for one of the reported germline risk alleles in EGFR or ERBB2. At our center, tumor NGS is performed using a hybrid-capture platform spanning exons and key introns of ~400 cancer related genes, and is available for patients (pts) with consent to a research protocol. For living pts with a mutation detected at an allelic fraction (AF) &gt; 25%, and excluding acquired T790M, genetic counseling and CLIA germline testing was provided. For pts with EGFR T790M, testing was performed on the INHERIT EGFR study (NCT01754025; ALCMI). Results: 51 cases were identified from a total of 13,488 cancers with NGS results: 45 with EGFR T790M (all lung cancer), 4 with EGFR R776H (NSCLC, endometrial cancer, and 2 glioma), 2 with ERBB2 G660D (NSCLC and glioblastoma). 34 pts with T790M detected after EGFR inhibitor were excluded, leaving 17 pts of interest. Germline testing was performed on 9 living pts with &gt; 25% AF on NGS, and was positive in 8; 6 of these had germline EGFR T790M. Additionally, germline EGFR R776H was found in a never-smoker with metastatic endometrial cancer; she had a prior a history of NSCLC, and family history was notable for multiple members with lung, breast, and colon cancer. Germline ERBB2 G660D was found in a young never-smoker with metastatic NSCLC and a family history significant for lung cancer in multiple first-degree relatives. Conclusions: Rare germline lung cancer risk mutations in EGFR and ERBB2 can be identified on routine tumor NGS, and may indicate a risk of inherited lung cancer. Our study includes the second known report of a germline EGFR R776H or ERBB2 G660D mutations. Commercial germline NGS assays could be expanded to cover these rare but potentially high-penetrance variants.
Breast cancer specific quality of life in HR+/HER2- advanced/metastatic breast cancer patients in a real-world setting.
Authors: Robert Wood, Debanjali Mitra, Jonathan De Courcy, Shrividya Iyer
Journal: Journal of Clinical Oncology (2016)

554 Background: To assess patient reported breast cancer (BC) specific quality of life (QOL) in HR+/HER2- advanced or metastatic BC (ABC/MBC). Methods: Patients (N=2,352) were recruited into a cross-sectional survey from centers in 5 major EU countries and the US. BC specific QOL was reported by a subset of patients (n=739) using the Functional Assessment of Cancer Therapy Breast (FACT-B) tool, which includes the FACT General (FACT-G) (4 subscales assessing physical [PWB], social [SWB], emotional [EWB], and functional [FWB] wellbeing) and the BC specific subscale (BCS). Results are reported for the overall cohort, by therapy and sites of metastases. Significance was assessed using Mann-Whitney U and Kruskal-Wallis tests. Results: Patients’ mean (SD) age was 65.2 (10.6). Most patients (82.7%, n=611) had MBC, of which 31.9% had bone only metastases, 39.6% visceral only, 18.0% had bone + visceral, and 10.5% had other metastasis sites. Most patients received either endocrine or chemotherapy (46.3% and 48.6%), while 3% were on both and 2.2% on neither therapy. Mean (SD) scores for FACT-G and FACT-B were 61.8 (15.8) and 85.9 (19.7) respectively. FACT scores stratified by current therapy and sites of metastases are in the table below. Significantly (p<0.05) better scores were reported in endocrine therapy patients compared to chemotherapy for all subscales. Significantly worse scores were reported in the bone + visceral group for all subscales except for SWB and FWB. Conclusions: Type of therapy and sites of metastases have a significant impact on patient reported BC QOL in HR+/HER2- ABC/MBC. Current Therapy Sites of Metastases Endocrine (n=342) Chemotherapy (n=359) Bone Only (n=195) Visceral Only (n=242) Bone + Visceral (n=110) PWB 19.9 (5.7) 18.0 (5.0)* 19.1 (5.5) 18.7 (5.5) 17.1 (5.4)* SWB 17.9 (6.0) 17.1 (5.2)* 17.7 (5.8) 16.9 (5.9) 17.0 (5.2) EWB 13.7 (4.6) 12.8 (4.2)* 13.7 (4.5) 13.1 (4.6) 12.0 (4.3)* FWB 13.6 (5.9) 12.1 (4.8)* 13.1 (5.8) 12.5 (5.5) 11.8 (4.9) BCS 25.2 (5.9) 23.2 (5.1)* 25.0 (5.7) 23.7 (5.6) 22.2 (5.6)* FACT-G Total 65.0 (17.3) 59.8 (13.1)* 63.7 (16.3) 60.9 (15.8) 57.7 (15.1)* FACT-B Total 90.4 (21.3) 83.1 (16.4)* 88.7 (20.4) 84.8 (19.4) 79.7 (18.6)* * P<0.05. Visceral = brain, liver, lung, pancreas.
Ten-year trends in acute hospital activity related to gastrointestinal infection
Authors: GA Doherty, CF DeGascun, EG Smyth, FE Murray
Journal: Endoscopy (2006)

Aims: Recent studies have highlighted the impact of gastrointestinal infections in Ireland (1.5 million working days lost annually). We analysed National HIPE data returns from 1994–2003 as they related to intestinal infections to assess the impact of these disorders on acute hospital activity.
Next-Generation Sequencing Analysis Revealed That BCL11B Chromosomal Translocation Cooperates with Point Mutations in the Pathogenesis of Acute Myeloid Leukemia
Authors: Antonella Padella, Giorgia Simonetti, Viviana Guadagnuolo, Emanuela Ottaviani, Anna Ferrari, Elisa Zago, Francesca Griggio, Marianna Garonzi, Giulia Paciello, Simona Bernardi, Carmen Baldazzi, Cristina Papayannidis, Maria Chiara Abbenante, Francesca Volpato, Raffaele Calogero, Nicoletta Testoni, Elisa Ficarra, Alberto Ferrarini, Massimo Delledonne, Ilaria Iacobucci, Giovanni Martinelli
Journal: Blood (2014)
Long term follow up of patients with locally advanced triple negative breast cancer treated with adjuvant high dose chemotherapy and autologous stem cell transplantation: A single center experience.
Authors: Sani Mohammed Bukari, Muhammad Usman, Judith Abrams, Voravit Ratanatharathorn, Joseph P. Uberti, Abhinav Deol, Divaya Bhutani, Asif Alavi, Lois Jeanne Ayash
Journal: Journal of Clinical Oncology (2017)

e12590 Background: Adjuvant high dose chemotherapy (HDC) with Autologous Hematopoietic Stem Cell Transplantation (AuSCT) as part treatment of high risk locally advanced breast cancer has remained controversial. Multiple trials reported disease free survival (DFS) without Overall survival (OS) resulting in its abandonment in early 2000s. However, post hoc analysis of these trials consistently reported DFS and OS benefit in young and triple negative breast cancer (TNBC) subgroups. This has not been re-evaluated till date. Recent European registry reports coupled with improved transplant related mortality (TRM) and still poor out-come of standard of care in TNBC subgroup has generated renewed interest. We report long term out-come of locally advanced high risk TNBC treated with HDC and AuSCT treated in Karmanos Cancer Institute from 1995 to 2001 Methods: Majority of the patients were treated with Adriamycin and Taxane based induction chemotherapy. Patients without evidence of metastatic disease proceeded to HDC and AuSCT using Carmustine 600mg/sqm Cyclophosphamide 5.6gm/sqm and Cisplatin 165mg/sqm (STAMP 1 regimen). This is followed with loco- regional radiation per protocol. Results: 72 hormone negative patients with Lymph Node(LN) &gt; 4 or inflammatory breast cancers were selected from 576 treated for advanced or metastatic breast cancer. 33 patients were TNB with HER2 status of 39 patients unknown. Median time from diagnosis to stem cell transplantation was 6 months. Median age at diagnosis was 47yrs. Mean LN involvement was 9 with 90% having (4-20) LN positivity. With median follow up of 16 years,10yrs DFS and OS were both 62.5%. Median follow up for DFS and OS was not reached.TRM was 9% mostly from pulmonary toxicity. Conclusions: This study of locally advanced high risk TNBC treated with adjuvant HDC and AuSCT have high 10yr OS of 62.5% compared to current standard of care. With the current improvement in TRM, reevaluation of this strategy through clinical trials in this subgroup whose outcome remain poor is reasonable.