tbuckley/cabot-search huggingface dataset:
A pilot feasibility study of gefitinib (ZD1839) and celecoxib in metastatic GI tumors
Authors: N. H. Yamaguchi, I. A. Mayer, A. Malzyner, C. J. C. Andrade, A. M. Murad, A. D. Giglio, H. Cardoso
Journal: Journal of Clinical Oncology (2004)

3086 Background: Gefitinib (‘Iressa’, ZD1839) is an EGFR-TKI (tyrosine kinase inhibitor) and celecoxib is a COX2 inhibitor with anti-inflammatory, anti-angiogenic, and anti-proliferative properties. In the early development of gefitinib, anecdotal responses were reported in GI tumors. Celecoxib (400 mg bid) has demonstrated activity in colorectal polyposis (Steinbach G, NEJM 2000). We hypothesized that the inhibition of both EGFR and COX2 are potential therapeutic targets in GI tumors. To date, the clinical use of this combination has not been reported in GI malignancies. Methods: A multicenter feasibility study of gefitinib 250 mg/day and celecoxib 400 mg bid was carried in patients with advanced GI malignancies. 16 men and 14 women with a median age of 58 years were recruited. All patients had more than one previous chemotherapeutic treatment. Primary tumors consisted of 25 colorectal, 3 pancreatic, 1 esophageal, and 1 gallbladder. All patients were enrolled in 2002 and 2003 and had signed an informed consent approved by the central IRB . All patients had available paraffin blocks for IH analysis on EGFR and COX2 expression. Results: By RECIST criteria, 3 patients (2 with colorectal cancer and 1 with pancreatic cancer) had confirmed stable disease and 27 patients had progressive disease. Adverse events (AEs) were generally mild and consisted mainly of acne, diarrhea, and nausea. No grade 3/4 AEs were reported. Dose reductions for celecoxib (to 200 mg bid) were reported for 5 patients due to gastrointestinal toxicity. Data on EGFR and COX2 expression in paraffin blocks will be presented at a future date. Conclusions: In chemotherapy refractory pretreated patients with advanced GI cancers, the combination of gefitinib and celecoxib is feasible and generally well tolerated. Further studies to identify a subgroup of patients that would benefit from this combination are warranted. ‘Iressa’ is a trademark of the AstraZeneca group of companies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Hepatic trans-arterial chemoembolization (TACE) in metastatic breast cancer.
Authors: Silvia Damian, Anna Tessari, Giuseppe Capri, Paola Mariani, Giulia Valeria Bianchi, Gabriella Mariani, Francesca Ricchini, Lorenzo Sica, Elena De Benedictis, Sara Cresta, Rodolfo Lanocita, Carlo Spreafico
Journal: Journal of Clinical Oncology (2013)

e12017 Background: Liver metastasis is one of the most frequent cause of death in breast cancer patients. Among loco-regional approaches available for solid tumor liver metastasis, TACE allows a prolonged intra-lesion exposure to chemotherapeutic agents. Initial studies have highlighted a benefit in terms of response rate (RR) and overall survival (OS) in breast cancer patients treated with TACE versus systemic chemotherapy. Methods: We have retrospectively evaluated 14 patients affected by breast cancer with liver metastasis. Patients had been selected for liver TACE according to the presence of liver metastasis as only site of disease, or in the event of further sites of metastasis that were stable or in response from the previous treatment. All the patients received one or more TACE with DC-Bead (Biocompatibles UK) 100-300 micron, loaded with a chemotherapeutic agent (doxorubicin, paclitaxel).The systemic therapy received by patients before TACE could be confirmed or changed according to disease response. Objective of the study was to evaluate the response rate to TACE and its correlation with the response to the very last treatment performed before it. As surrogate of efficacy, time to progression (TTP) and OS were analyzed. Results: Among the 14 treated patients (5 heavily pretreated, with more than three lines of chemotherapy) only one obtained a complete remission (RC). Four patients presented a partial remission (PR). Three of them were progressing from previous treatment and one had a PR. Stable disease (SD) after TACE was obtained in four cases: two of them had a progressive disease (PD) before TACE and two had a responsive disease. Five patients did not respond to TACE (one with PR from the previous line of therapy). Median TTP observed in responsive patients (CR + PR) was 4.5 times higher than non-responders (PD) (13.2 vs. 2.9 months). Patients with SD had a median TTP of 4.3 months. Median OS of responsive patients was 25.6 months vs. 17.5 and 19.2 months of patients with SD or PD respectively. Conclusions: In our experience, chemoembolization can represent a valid therapeutic option in breast cancer patients with liver metastasis, independently from the response to the previous systemic therapy, and may prolong survival.
Radiographic extracapsular extension (ECE) and treatment outcomes in locally advanced oropharyngeal carcinoma (OPC).
Authors: Benjamin H. Kann, Michael Buckstein, Todd J. Carpenter, Ava Golchin, Richard Lorne Bakst, Krzysztof Misiukiewicz, Eric Michael Genden, Marshall R. Posner, Lale Kostakoglu, Peter M. Som, Vishal Gupta
Journal: Journal of Clinical Oncology (2013)

6019 Background: Pathologic ECE (pECE) of tumor through lymph node (LN) is a poor prognosticator for OPC and typically diagnosed upon surgical LN removal. At our institution, experienced radiologists routinely identify ECE on pretreatment CT. The prognostic value of radiographic ECE (rECE) is less clear and may prove clinically useful. In this study, we evaluate rECE as an independent prognosticator in OPC. Methods: Retrospective review of 185 patients with locally advanced OPC treated in our department from 2006-2012. 109 patients had accessible pretreatment CT reports clearly stating the presence or absence of rECE. Patients were treated with definitive concurrent chemoradiation therapy (CCRT) (30%), induction chemo then CCRT (47%), or surgery with adjuvant CCRT (14%) or RT (9%). Kaplan-Meier survival analysis compared these cohorts for locoregional control (LRC), distant control (DC), and progression-free (PFS) and overall survival (OS); log-rank tests were performed for significance. Multivariate analysis was conducted via cox-regression. Results: Median follow-up of the 109 patients was 31 months (range: 1-80 months). 61 patients had rECE(+) and 48 had rECE(-) scans. There was no significant difference between the cohorts in terms of median age, stage, treatment type, smoking history, or tumor HPV status. There was a difference in nodal stage with 83% of rECE(+) patients having N2-3 disease versus 67% of rECE(-) patients (p=0.02). On univariate analysis, there were differences between the rECE(-) versus rECE(+) cohorts in OS (4yr: 92% vs 72%, p=0.01), PFS (4yr: 92% vs 62%, p=0.002), and DC (4yr: 98% vs 76%, p=0.006), with no difference in LRC (4yr: 95% vs 91%, p=0.35). On multivariate analysis factoring in age, smoking history, stage, and treatment type, rECE presence was a negative predictor of OS (hazard ratio, 0.26; 95% CI, 0.07 to 0.95) and PFS (hazard ratio, 0.23; 95% CI, 0.06 to 0.81), with DC approaching significance (hazard ratio, 0.13; 95% CI, 0.02 to 1.05). Conclusions: While pECE is an established risk factor for locally advanced OPC, this study suggests that rECE may be an independent poor prognosticator of PFS, OS and DC with potential importance in guiding clinical management.
Malignant pleural mesothelioma: new treatments, new hopes?
Authors: Arnaud Scherpereel
Journal: European Respiratory Journal (2017)

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour type arising from the mesothelial surface of the pleural space. MPM is difficult to treat and commonly associated with asbestos exposure, which is its main risk factor [1]. In Europe, the incidence is about 20 per million, with large inter-country variation [2]. As a ban on the use of asbestos was proposed quite recently in most countries, and the median latency between asbestos exposure and MPM onset is about 40 years, incidence rates in some European nations are still rising, with peak incidences expected around 2020 and beyond. Moreover, asbestos continues to be used in many developing and emerging countries of the world, suggesting a potential mesothelioma epidemic in the future. The clinical signs are usually late and nonspecific. Chest computed tomography scanning, a key imaging procedure in MPM, usually shows unilateral pleural effusion, sometimes combined with pleural thickening [1, 3]. New tools may select mesothelioma patients who can benefit from promising therapeutic multimodal strategies <http://ow.ly/yp8W309tg0i>
HER2 quantification by mass spectrometry compared to IHC or ISH in predicting clinical benefit from anti-HER2 therapy in HER2-positive breast cancer (BC).
Authors: Paolo Nuciforo, Claudia Aura, Sheeno P Thyparambil, Marta Vilaro, Ana C. Garrido-Castro, Vicente Peg, Jose Jimenez, William Arthur Hoos, Jon Burrows, Todd A. Hembrough, Jose Manuel Perez-Garcia, Javier Cortes, Maurizio Scaltriti
Journal: Journal of Clinical Oncology (2015)

605 Background: To be eligible for an anti-HER therapy, tumors have to be HER2-positive as determined by IHC or in situ hybridization (ISH) analyses. Although gene amplification is generally considered the main mechanism of HER2 protein overexpression in BC, the biologic regulation of HER2 expression is complex and gene amplification may not always correlate quantitatively with HER2 protein levels and with response to anti-HER2 therapies. Methods: HER2-positive (n = 123) primary BC samples were microdissected, solubilized and digested in trypsin in Liquid Tissue buffer. Absolute quantitation for HER2 protein was performed using selected reaction monitoring (SRM) mass spectrometry. ISH was centrally performed on all cases. HER2 gene copy number (GCN), HER2/Chr17 ratio, and pattern of amplification were evaluated and correlated with HER2 protein levels. The survival benefit according to protein and gene levels was calculated for patients receiving an adjuvant anti-HER2 therapy (n = 68). Results: HER2 SRM levels showed weak positive correlations with HER2 GCN and HER2/Chr17 ratio. Average HER2 protein levels were significantly higher in tumors amplified with homogeneous stained regions (HSR, n = 50) compared to those with double minutes (DM, n = 46). Ten amplified cases showed HER2 protein levels similar to HER2-negative tumors. Eight had a DM and 2 a mixed pattern of amplification. None was amplified in HSR. HER2 protein levels > 2,200 amol/µg predicted better disease-free survival and overall survival in patients treated with adjuvant trastuzumab. Neither HER2 GCN, HER2/Chr17 ratio nor pattern of amplification correlated with outcome. Conclusions: By using an objective non-antibody based method we identified a great deal of disparity of HER2 levels in BC patients that are classified as HER2-positive by ISH. Different amplification patterns resulted in significantly different protein levels; with many cases of DM amplification showing no concomitant increase in HER2 protein expression. Our findings indicate that protein abundance rather than gene status predict the clinical benefit from anti-HER2 therapy in HER2-positive BC patients.
Trends in the use of adjuvant therapy for women with breast cancer under age 65.
Authors: Filipa Lynce, Arnold L. Potosky, Sandra M. Swain, Nandini Selvam, Claudine Isaacs
Journal: Journal of Clinical Oncology (2015)

e17541 Background: There is a paucity of data describing the use of systemic adjuvant treatment for US women under age 65 with breast cancer (BC) treated in community practice. Trends and patterns in use of cancer treatments by sociodemographic factors accounting for variations sorted by clinical subtype have rarely been assessed for this age group. We assessed recent trends in the use of endocrine therapy (ET) and chemotherapy (CT) prescribing patterns. Methods: We identified 13,456 insured women under age 65 diagnosed with stage I-III BC between 2006-2011 from a newly created linked dataset consisting of cancer registry data and health claims data. It includes five state cancer registries (CA, GA, KY, NY, OH) containing clinical and pathological variables linked with claims data maintained by HealthCore Inc. (Wilmington, DE), an independent subsidiary to Anthem, Inc., an independent licensee of the Blue Cross and Blue Shield Association. Multiple logistic regression analysis was used to assess the independent contributions of sociodemographic factors to the use of therapies. Results: Of 13,456 women identified, 49% presented with stage I, 38% with stage II and 13% with stage III. In the entire cohort there was a steady decline in the use of CT over time from 53% in 2006-07 to 43% in 2010-11 (p < .001), and with increasing age (71% of women ages 24-39 declining to 40% of women ages 60-64, p < .001). Among those receiving CT, use of anthracycline-based regimens decreased from 69% in 2006-07 to 42% in 2010-11 (p < .001), a decline that persisted after adjusting for all other factors. In those with hormone positive (HR+) disease, only 78% initiated ET within 18 months of diagnosis. Initiation of ET declined over time, from 81% in 2006 to 76% in 2011 (p < .001). Nine percent of women ages 24-39 with HR+ disease did not receive any adjuvant ET or CT. All comparisons were statistically significant after adjustment for all other factors. Conclusions: In an insured population cohort of women under age 65, we observed an overall decrease in CT and ET, and a shift away from use of anthracyclines over time. These results provide new insights regarding recent temporal trends and community-based practice patterns of adjuvant systemic therapies for women diagnosed with stage I-III BC.
Radiographic assessment and therapeutic decisions at RECIST progression in EGFR-mutant NSCLC treated with EGFR tyrosine kinase inhibitors.
Authors: Mizuki Nishino, Stephanie Heon, Suzanne Eleanor Dahlberg, David Michael Jackman, Nikhil H. Ramaiya, Hiroto Hatabu, Michael S. Rabin, Pasi Antero Janne, Bruce E Johnson
Journal: Journal of Clinical Oncology (2012)

7553 Background: EGFR mutated advanced NSCLC treated with EGFR TKIs typically progresses after initial response due to acquired resistance. TKI therapy is often continued beyond RECIST progression (PD). We investigated the frequency of this practice and patterns of RECIST PD via imaging findings, as well as the association between patient characteristics and discontinuation of TKI among patients (pts) who progressed while on TKI. Methods: Among a cohort of 101 advanced NSCLC pts with sensitizing EGFR mutations treated with first-line erlotinib or gefitinib at DFCI, 70 pts treated between 2002 and 2010 had at least two CT scans for retrospective radiographic assessments using RECIST1.1; 56 pts had experienced PD by the data closure date of June 2011. Results: Among 56 pts experiencing PD, 46 (82%) were female, median age was 63 (range 35-79), 28 (50%) were never-smokers, 32 (57%) had distant mets, 32(57%) had exon 19 deletion, and 50 (89%) received erlotinib. 49 pts (88%) continued TKI therapy for at least 2 mos beyond retrospectively assessed PD. 31/32 (97%) pts who progressed by increase of target lesions continued TKI. 13/16 (81%) pts who progressed by new lesion remained on TKI. Two pts with PD in non-target lesions discontinued therapy at PD. 5/6 (83%) pts with both increase of target lesions and new lesion at PD continued TKI. In 49 continuing pts, the median time from RECIST PD to termination of TKI was 10.1 mos (range: 2.2-64.2 mos). 15/49 (31%) pts who continued TKI received additional chemo compared to 0/7 pts who discontinued (Fisher’s p=0.17). Pts who discontinued therapy (n=7) were significantly younger (median 48 yrs) than those who continued TKI at PD (median 64 yrs, Wilcoxon p=0.003). Median OS beyond RECIST PD among those who continued TKI was 31.8 mos (95% CI 15.9- not reached) and though underpowered, this did not appear to be impacted by TTP when adjusted in a Cox model (p=0.84). Conclusions: 88% of EFGR-mutant NSCLC pts who progressed on first-line TKI continued therapy beyond RECIST PD, which is not the single determining factor for terminating TKI in EGFR-mutant NSCLC pts. Additional progression criteria specific to this population are needed to better guide therapeutic decision making.
NACT in locally advanced oral cancers : Does HPV make a difference?
Authors: Vijay Maruti Patil, Shubhada Kane, Vanita Noronha, Amit Joshi, Sachin Dhumal, S Juvekar, Supreeta Arya, Suyash Kulkarni, Atanu Bhattacharjee, Kumar Prabhash
Journal: Journal of Clinical Oncology (2015)

e17068 Background: HPV positive oropharyngeal cancers have been identified as a favourable prognostic subgroup. However impact of HPV positivity on prognosis is also dependent on level of tobacco exposure and on stage of the disease. We wanted to study the impact of HPV in locally advanced and very locally advanced technically inoperable oral cancers undergoing neoadjuvant chemotherapy (NACT) Methods: This was a retrospective analysis of 124 randomly selected patients who underwent NACT at our centre between 2012 to 2013. All of these patients had locally advanced technically unresectable oral cancers ( Stage IVA or IVB disease) and they underwent 2 cycles of NACT followed by response assessment. Depending upon the response these patients either underwent radical intent treatment ( Surgery + adjuvant chemoradiation (CTRT) or radical CTRT or palliative intent treatment ( Palliative RT or Palliative chemotherapy or supportive care).Subsequently these patients were followed till death. p16 IHC was done on the pretreatment biopsy for identifying HPV positive tumors. The post NACT response rate ( in accordance with RECIST version 1.1) was compared between the HPV positive and HPV negative cohort by proportion test. The Overall survival (OS) between HPV positive cohort and HPV negative cohort was compared by log rank ( Mantel-Cox) test. Cox Proportional Hazard regression model was applied to identify factors affecting OS. Results: Out of the 124 patients selected, 18 patients were HPV positive. (14.5%). In HPV positive cohort 27.8 % ( 5 patients , n = 18 ) patients responded to NACT while in HPV negative cohort it was 28.3% ( 30 patients, n = 106 )(p = 1).The locoregional failure rate was 33% in HPV positive patients while it was 47.2 % in HPV negative patients. (p = 0.40). The 2 year OS was 45% (95% CI 36-54%) in HPV negative cohort while it was 82% (95% CI 60.8%-94.1%) in HPV positive cohort(p = 0.04). On COX regression analysis the only factor which affected OS was surgery. ( HR : 0.3; 95% CI 0.1- 0.6 ). HPV positivity had a trend towards impact on OS ( p = 0.07). Conclusions: HPV positive technically unresectable oral cancers seem to have better overall survival. Prospective study to validate this results are needed.
What do 676 primary and recurrent ovarian cancer (OC) patients expect from their doctors and therapy management? Results of a German survey of the northeastern German Society of Gynecological Oncology (NOGGO).
Authors: Gülten Oskay-Özcelik, Radoslav Chekerov, Sylvia Neubert, Karsten Münstedt, Hans-Joachim Hindenburg, Clemens Liebrich, Lars Christian Hanker, Ralf Lorenz, Pauline Wimberger, Jalid Sehouli
Journal: Journal of Clinical Oncology (2012)

5044 Background: The primary aim of this study was to investigate information needs and preferences among patients with ovarian cancer, focusing especially on doctor-patient relationships and therapy management. Methods: A 42-item questionnaire was developed and validated in a mono-centre phase I study and was then provided to primary and recurrent ovarian cancer patients via internet (online) or as a print-version. In the first part basic data (age, tumour status, therapy) were requested. In the second part, most of the questions try to evaluate the expectations and needs concerning their therapy management and doctor-patients communication. Results: From January to November 2009, a total of 676 (201 online; 475 print version) patients with ovarian cancer from 44 German centres took part in the survey.The median age of the online group was 49 years (range 19-84), for the print group 62 years (26-92). Nearly all patients (98.7%) had a primary surgery and a primary chemotherapy (89%). Asked for side effects during therapy, the most frequent answers were alopecia, paraesthesia/dysaesthesia and fatigue. Most of the patients were content with the completeness and understandability of the explanations about the therapies from their doctors . The three most important aspects, which were proposed by patients to improve therapy against ovarian cancer were: “Doctors should have more time for explanations”, “The therapy should not lead to any loss of hair”, and “The therapy should be more effective”. Conclusions: This study underlines the high need of ovarian cancer patients to discuss all details concerning treatment options and clinical management. As matter of fact, the physician involved in the treatment is the most important source of information.
Pre-analytics optimization of non-invasive plasma specimens to improve <i>KRAS</i> mutation (<i>KRAS</i>m) detection in patients with non-small cell lung cancer (NSCLC).
Authors: James Sherwood, Alan Sharpe, Claire Corcoran, Helen Brown, Milena Musilova, Jill Walker, Alexander Kohlmann
Journal: Journal of Clinical Oncology (2015)

e22150 Background: Non-invasive KRASm testing using circulating tumor DNA (ctDNA) extracted from blood is a promising companion diagnostic option, which could enable patients with NSCLC but no available tumor sample to access more treatment options. Methods: Peripheral blood samples were collected from 34 patients with NSCLC. The impact of pre-analytical processing, including sample collection tube (EDTA vs cell-free DNA blood collection tube [BCT, Streck]), incubation time at room temperature (2 vs 72h) and centrifugation steps (single vs double spin), was investigated. The use of alternative input plasma volumes was also assessed. Recovery of DNA (QIAamp Circulating Nucleic Acid Kit) was evaluated by qPCR; KRASm analysis was performed using the Therascreen KRAS RGQ PCR kit (QIAGEN). Results: Two-way analysis of variance of log-transformed data showed sample collection tube and plasma processing time had a significant effect on DNA yield (p < 0.01 for both factors) with EDTA collection tubes and longer incubation times associated with increased DNA yield (mean [untransformed], SD): EDTA/2h (2.49 ng/μL, 1.60), EDTA/72h (15.12 ng/μL, 16.44), BCT/2h (2.39 ng/μL, 1.42), BCT/72h (3.31 ng/μL, 1.82). Regression analysis of log-transformed data showed a significant increase in DNA yield with increasing sample volume (slope = 0.45; p-value = 0.01) (mean [untransformed], SD): 3 mL (4.39 ng/μL, 4.55), > 2 mL (3.03 ng/μL, 3.24), > 1 mL (1.79 ng/μL, 1.81). “BCT, 2h, double spin” was selected as the preferred method; lower DNA yields indicated improved blood cell stabilization, therefore reducing contaminating genomic DNA. Application of this method translated into an improvement in KRASm detection: of 10 cases with known KRASm in FFPE tissue, 5/10 (50%) were detected as KRASm in plasma, compared to 2/10 (20%) using non-optimal methods (EDTA collection tubes and 72h). Conclusions: This study demonstrated that successful ctDNA recovery for KRAS detection is strongly dependent on pre-analytical processing steps. Standardized methods could significantly improve the detection rate of KRASm from ctDNA specimens.
Focusing on the role of endoscopy in chronic pancreatitis management – taking nature’s help
Authors: Amit Maydeo, Vinay Dhir
Journal: Endoscopy (2017)

Chronic pancreatitis is a multifactorial inflammatory condition of the pancreas characterized by recurrent or persistent episodes of abdominal pain and associated with exocrine or endocrine insufficiency. The etiology and presentation, as well as patients' pancreatic ductal morphology, vary considerably in different parts of the world.