tbuckley/cabot-search huggingface dataset:
RAMSETE: A single-arm, multicenter, single-stage phase II trial of RAD001 (everolimus) in advanced and metastatic silent neuro-endocrine tumours in Europe.
Authors: Marianne E. Pavel, Bertram Wiedenmann, Jaume Capdevila, Nicholas Reed, Juan W. Valle, Silvia Caglio, Christoph May, Silvia Comis, Ramon Castellana, W.W. de Herder, Cornelia Metzner, Ramon Salazar, Dieter Hörsch, Kjell E. Oberg
Journal: Journal of Clinical Oncology (2012)

4122 Background: The mammalian target of rapamycin (mTOR) signaling pathway is involved in the pathogenesis of neuroendocrine tumors (NET). Everolimus (RAD001), an oral mTOR inhibitor, has antitumor activity in patients (pts) with advanced NET. In this open-label, multicenter, phase II study (RAMSETE), the safety and efficacy of everolimus monotherapy was evaluated in pts with advanced nonsyndromic, nonpancreatic NET. Methods: Pts with advanced (unresectable or metastatic), progressive, nonsyndromic, nonpancreatic NET received everolimus (10 mg/day) as monotherapy. The primary endpoint was objective response rate (proportion of pts with best overall complete response [CR] or partial response [PR] per RECIST v1.0) by central radiologic review. A secondary endpoint included progression-free survival (PFS). Results: By database soft lock (December 1, 2011), 73 pts from 16 European clinics received everolimus (median duration of treatment: 193 days). Fifty-five (75%) pts discontinued; reasons included disease progression (n=23), adverse events (AEs [n=23]), withdrawal of consent (n=4), death (n=3), and protocol deviation (n=2). In the per protocol population (N=60), 32 (53%) pts received prior antineoplastic therapy. The best response by central review was stable disease in 55%. By local review, 3 (5%) pts had a PR, with SD in 39 (65%) pts. Median PFS by central review was 185 days (95% CI: 158-255). Median PFS by local investigator review was 285 days (95% CI: 231-not estimable). 69 (95%) pts reported treatment-related AEs of any grade, including rash (n=28; 38%), diarrhea (n=20; 27%), mucosal inflammation (n=18; 25%), and decreased appetite (n=17; 23%). Treatment-related grades 3 and 4 AEs and serious AEs were reported by 27 (37%) and 18 (25%) pts, respectively. Conclusions: In this open-label trial of everolimus in pts with advanced, nonsyndromic, extrapancreatic NET, a high rate of disease stabilization was achieved after prior tumor progression with favorable median PFS. This study further supports efficacy of everolimus in types of NET other than those studied in RADIANT-3 (pancreatic NET) and RADIANT-2 (NET associated with carcinoid syndrome).
Being overweight at any point increases risk for death
Authors: Jacqui Wise
Journal: BMJ (2017)

People who are obese or overweight at any point in their adult lives are at greater risk of death from cardiovascular disease, cancer, and other causes than those who maintain a normal weight, according to an analysis of data from three large cohort studies published in Annals of Internal Medicine .1

The researchers said that looking at a person’s weight history reverses the paradoxical association between overweight and reduced mortality seen in some studies. A meta-analysis published in 2013 in JAMA had extensive media attention when it concluded that people who were overweight had a lower risk for death than those …
eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-Free DNAs in Blood
Authors: Jinfeng Zou, Edwin Wang
Journal: Genomics Proteomics & Bioinformatics (2017)

With the technology development on detecting circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs) of the cancer founding clone. eTumorType integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. eTumorType has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. eTumorType produced high accuracies (0.86-0.96) and high recall rates (0.79-0.92) for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies (0.78-0.92) and recall rates (0.58-0.95) have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that eTumorType could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cfDNAs.
Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial
Authors: N J Bahlis, A Corso, L-O Mugge, Z-X Shen, P Desjardins, A-M Stoppa, O Decaux, T de Revel, M Granell, G Marit, H Nahi, H Demuynck, S-Y Huang, S Basu, T H Guthrie, A Ervin-Haynes, J Marek, G Chen, T Facon
Journal: Leukemia (2017)

The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ⩾very good partial response (VGPR; n=679), ⩾partial response (PR; n=1 225) or ⩽stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ⩾VGPR and ⩾PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ⩾VGPR and ⩾PR, respectively. In patients with CR, ⩾VGPR or ⩾PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.
A new hepatic artery infusion model
Authors: J. G. Touzios, K.-H. Lee, J. Safron, W. Schulte, R. Ausman
Journal: Journal of Clinical Oncology (2004)

3660 Background: The role of hepatic artery infusion (HAI) has been controversial, and its use often has been empiric without the benefit of pharmacologic and toxicologic data because a suitable animal model that incorporates prolonged HAI has not been available. The goal of this study is to develop an HAI model nearly identical to humans and to employ this model to evaluate hepatic toxicity for site directed chemotherapy. In such a model, various tumor agents other than the traditional FUDR could be evaluated rapidly for dose determination and timing of administration. Methods: The Yucatan minipig possesses a cytochrome P450 enzyme family with remarkable similarities to the human and microscopic and gross anatomy that also resembles the human liver. In this development program, an hepatic artery catheter was placed via the gastroduodenal artery (GDA) in eight pigs. Continuous infusion of saline was maintained for one to four weeks to establish baseline information. Liver biopsies were done at the time of laparotomy for catheter placement and subsequently laparoscopic biopsies were performed at various intervals. Morphological evaluation of the organ was accomplished using light and transmission electron microscopy (TEM) and biochemically by direct measurment of P450 activity. Serum liver function studies were included in the overall assessment. Results: We were able to maintain an HAI catheter in the GDA for extended infusion periods to simulate human chemotherapy treatment protocols. Infusion of saline via HAI established baseline controls of TEM, light microscopy histology, and P450 activity levels. Data will be reported for these controls and some experimental animals. Conclusions: This HAI animal model allows for evaluation of hepatic toxicity of various cytotoxic agents at the cellular, subcellular, and biochemical level. Adverse interactions between drugs being administered simultaneously with hepatic artery infusion and susceptible to metabolic transformation by the P450 enzyme system can be identified readily with this model. It may be possible to study the underlying causes of sclerosing cholangitis commonly associated with FUDR. Supported by the Falk Medical Trust and Baxter International No significant financial relationships to disclose.
Invasion Science: A Horizon Scan of Emerging Challenges and Opportunities
Authors: Anthony Ricciardi, Tim M. Blackburn, James T. Carlton, Jaimie T.A. Dick, Philip E. Hulme, Josephine C. Iacarella, Jonathan M. Jeschke, Andrew M. Liebhold, Julie L. Lockwood, Hugh J. MacIsaac, Petr Pyšek, David M. Richardson, Gregory M. Ruiz, Daniel Simberloff, William J. Sutherland, David A. Wardle, David C. Aldridge
Journal: Trends in Ecology & Evolution (2017)
Outcomes in patients with liver or lung metastatic castration-resistant prostate cancer (mCRPC) treated with the androgen receptor inhibitor enzalutamide: Results from the phase III AFFIRM trial.
Authors: Yohann Loriot, Karim Fizazi, Johann Sebastian De Bono, David Forer, Mohammad Hirmand, Howard I. Scher
Journal: Journal of Clinical Oncology (2013)

5065 Background: Enzalutamide (ENZA) inhibits multiple steps in the androgen receptor signaling pathway (Tran et al, Science. 2009;324:787). The phase III AFFIRM trial demonstrated that ENZA increased median overall survival (OS) by 4.8 months (P &lt;0.001, HR 0.63) vs placebo (PBO) in post-docetaxel mCRPC patients (pts) (Scher et al, NEJM 2012; 367:1187). Here we assess the effect of ENZA on outcomes in pts with liver or lung metastases in the AFFIRM trial. Methods: The AFFIRM trial was a phase III multinational, randomized, double-blind study in post-docetaxel mCRPC pts. Randomization was 2:1 to ENZA 160 mg/day or PBO, stratified by baseline ECOG and mean pain score. The primary endpoint was overall survival (OS). Radiographic progression-free survival (rPFS) was a key secondary endpoint. PSA response defined as a decline of ≥50% compared to baseline, and soft tissue objective response per RECIST 1.1 were also assessed and reported here. Results: Pts with liver mCRPC comprised 11.5% (92/800) of ENZA pts and 8.5% (34/399) of PBO pts. Pts with lung mCRPC comprised 15.3% (122/800) of ENZA pts and 14.8% (59/399) of PBO pts. The median OS for patients with liver and/or lung mCRPC in the AFFIRM trial was 11.4 months (ENZA: 13.4 months; PBO: 9.5 months). Improved outcomes with ENZA treatment were observed in both liver and lung mCRPC pts. Conclusions: In the phase III AFFIRM trial, pts with lung mCRPC had higher median OS than pts with liver mCRPC. ENZA resulted in higher response rates in both liver and lung mCRPC pts. OS and rPFS were also improved in both pt groups treated with ENZA. Clinical trial information: NCT00974311. [Table: see text]
Genetic risk assessment in women with breast cancer in the outpatient setting: Establishing the standard of practice for ambulatory care clinics
Authors: S. Ethirajan, B. Adkins, S. Spencer, P. Gerken, N. Washburn, S. Simmons, V. Sommer, M. Rogers, A. Strauss Tranin
Journal: Journal of Clinical Oncology (2004)

1039 Background: Recognizing the importance of genetic information on the practice of oncology, ASCO has established guidelines for incorporating genetic information into clinical practice. The objective of this study was to assess how reliably genetic information is collected and used in practice. We identified and studied a population at risk of having an underlying genetic predisposition to cancer in the Kansas City metropolitan area. Methods: Chart audits on 210 women diagnosed with breast cancer at the KCCC clinics seen between January and February of 2002 were conducted by oncology nurses. All audited patients were under the age of 65 and were not currently undergoing chemotherapy treatment. A pedigree risk management tool was developed to examine the completeness of the family cancer history recorded, the frequency with which the patients were assessed for hereditary cancer risk, and the frequency with which they were considered for genetic counseling services. Results: Of the 210 charts reviewed, 85.5% of the charts audited had family history information of which 65.4 % reported 3 generations of family history while 14.5 % had no mention of family history. With respect to cancer risk management, 60.8 % reported risk management plans of which 9.8% required genetic counseling. The findings are summarized in the table below. Conclusion: These results suggest that a more careful assessment of hereditary cancer risk needs to be incorporated into medical practice. To improve access to genetic counseling for patients, we recommend that a family history questionnaire be incorporated into clinical practice as well as availing nurse practitioners and clinicians with educational programs designed to educate health practitioners on how to incorporate genetic information into clinical practice. No significant financial relationships to disclose.
Members of the glutathione (GSH) and ABC-transporter families are associated with clinical outcomes in patients with diffuse large B-cell lymphoma (DLCL)
Authors: C. Andreadis, P. A. Gimotty, P. Wahl, R. Hammond, J. Houldsworth, S. J. Schuster, T. R. Rebbeck
Journal: Journal of Clinical Oncology (2006)

10035 Background: Chemotherapy only cures 60–70% of DLCL patients (pts). While genes in both the GSH and ABC-transporter families have been implicated in drug resistance in other malignancies, their role in DLCL remains controversial. Methods: This study includes 94 DLCL pts with tissue expression data obtained prior to anthracycline-based chemotherapy from 2 oligonucleotide microarray datasets (Affymetrix) with annotated clinical information. Patient-level expression was derived for 10 key genes utilizing probe set matching and levels were adjusted for a common probe set signal. Freedom-from-progression (FFP) was analyzed using an accelerated failure-time regression model, stratified by the international prognostic index (IPI). CART software was used to develop a classification tree for the 2-year disease-free rate. Results: Based on IPI, 48% of pts were low risk, 23% were low-intermediate (int) risk, 24% high-int risk, and 12% were high risk. After therapy, 30 pts (32%) had disease relapse or progression within 2 yrs and 58 pts (62%) were disease-free; 6 (6%) had shorter follow-up. Expression of multi-drug resistance 1 (MDR1; ABCB1) was favorably associated with FFP (β=1.89, p=0.004), with a 100-point change in the expression signal resulting in a near-doubling of the time to failure (time ratio (TR) = 2.2, 95%CI: 1.3–3.6). Expression of GSH S-transferase μ, classes 1/2/4 (GSTM124) was also favorably associated with FFP (β=0.14, p=0.001); a 1000-point signal change resulted in a near-doubling of the time to failure (TR=1.8, 1.3–2.4). Based on our tree, 2 risk groups were identified using IPI and 3 genes: ABCB1, GSTM124, and GSH cysteine ligase modifier (GCLM). Thus, 89% (78%-96%) pts in the low-risk group (N=56) were disease-free at 2 yrs vs. 25% (11%-43%) pts in the high-risk group (p&lt;0.001). Conclusions: We observed a significant favorable association between expression of genes in the GSH and ABC-transporter families, and FFP in pts treated for DLCL. Moreover, we generated 2 risk groups based on the IPI and the expression of 3 key genes, which we plan to validate in an independent dataset. Our findings suggest an additional role for these genes that are classically associated with drug resistance. No significant financial relationships to disclose.
Estrogen withdrawal, breast cell transformation, and multiple breast cancer risk in women with the KRAS-variant.
Authors: Joanne B. Weidhaas, Terri Patricia McVeigh, Song Yi Jung, David Salzman, Sunitha Nallur, Michelle Dookwah, Antonia A Nemec, Jackie Sadofsky, Trupti Paranjape, Olivia Kelly, Elcie Chan, Nicola Miller, Karl J Sweeney, Daniel Zelterman, Joann Sweasy, Robert Pilarski, Donatello Telesca, Michael J. Kerin
Journal: Journal of Clinical Oncology (2015)

e12541 Abstract Background: The KRAS-variant is a functional, microRNA binding site variant that predicts increased cancer risk as well as response to cancer therapies. Here we evaluate the impact of estrogen exposure on breast cancer (BC) cell transformation, as well as BC risk and tumor biology in women with the KRAS-variant. We further study the association of this variant with multiple primary breast cancer (MPBC). Methods: The impact of estrogen withdrawal on transformation in isogenic breast epithelial cell lines with or without the KRAS-variant was studied. Women with BC (n= 1712) and KRAS-variant unaffected controls (n= 80) were recruited, and hormonal exposures, KRAS-variant status, and pathology were compared. Presentation characteristics of MPBC were also studied. Results: Isogenic lines with the KRAS-variant had unique biology, and acute estrogen withdrawal led to oncogenic transformation. Consistent with our biologic findings, KRAS-variant BC patients were significantly more likely to have oophorectomy pre-BC diagnosis than non-variant BC patients (p = 0.033). In addition, KRAS-variant BC patients appeared to have a lower estrogen state than KRAS-variant controls, with a lower BMI (p < 0.001). HRT discontinuation in KRAS-variant BC patients was significantly associated with a diagnosis of triple negative BC. Finally, KRAS-variant BC patients had greater than an 11-fold increased risk of MPBC compared to non-variant patients (45.39% vs 6.78%, OR 11.44 [3.42-37.87], p < 0.001). Conclusions: Estrogen withdrawal and a low estrogen state appear to increase BC risk and to predict aggressive tumor biology in women with the KRAS-variant. These women are also significantly more likely to present with a second, independent breast cancer.
Pemetrexed + cisplatin (DDP) in patients with malignant peritoneal mesothelioma (AbM)
Authors: M. Karthaus, D. Metzner, G. Maher, A. Plahl, N. Wert
Journal: Journal of Clinical Oncology (2004)

7201 Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the lining of the lung. Only case reports are available for treatment and outcome of AbM. Pemetrexed (ALIMTA™) is a novel antifolate targeting key enzymes in purine and pyrimidine synthesis. Recently data from a randomized phase III trial have shown superior efficacy of pemetrexed/DDP vs DDP alone in MPM, however, no data of pemetrexed in AbM are available. Methods: In an open label trial, efficacy and safety data of pemetrexed (500 mg/m2) +/-DDP (75 mg/m2) or carboplatin (AUC 5) were studied to obtain data for AbM and MPM. A total of 49 mesothelioma pts with stage III/IV were observed between 12/02 and 11/03. Pts received pemetrexed based therapy including dexamethasone prophylaxis for skin rash on day −1 to+2 additionally. Folic acid 400 μg po daily, prior to and during study, and vitamin B 12 1000 μg i.m. q 9 wks in addition was administered to prevent adverse events. Study endpoints were response (RR), time to progression (TTP) and safety. Results: Four pts (1 AbM, 1 MPM, 2 MPM+AbM) were excluded due to renal impairment (n=1) or death prior to chemotherapy (n=3). 45 mesothelioma pts (34 m/11 f) were treated with pemetrexed. Staging revealed AbM in 11 pts, MPM in 30 pts, while 4 pts had malignant mesothelioma on both sites of the diaphragma. Initial combination was with DDP in all pts with AbM, while this was DDP in 23, and carboplatin in 11 of the remaining 34 pts. Pemetrexed was administered a median of 6 cycles (range 1–13). Major toxicities (WHO >°III/IV) were nausea and neutropenia (2/11). Up to 11/03 death has been reported due to PD in 19 out of 49 pts, including 5 of 11 pts with AbM. Treatment and response data are given in the table below. Data regarding TTP will be presented at the meeting. Conclusions: Pemetrexed in combination with DDP is a well tolerable and active regimen for advanced peritoneal malignant mesothelioma. No significant financial relationships to disclose.
A person-centered e-proms multi-faceted intervention to improve patient experience and health outcomes: A multi-site implementation study in diverse ambulatory oncology practices.
Authors: Doris Howell, Madeline Li, Zeev Rosberger, Nicole Montgomery, Carole Mayer, Anne Snider, Denise Bryant-Lukosius, Marc Hamel, Rosanna Faria, Lorraine Martelli, Alyssa Macedo
Journal: Journal of Clinical Oncology (2017)

182 Background: The Improving Patient Experience and Health Outcomes Collaborative (iPEHOC) aims to improve health outcomes through uptake of electronic patient reported outcome measures (e-PROMs) in oncology practices in Ontario and Quebec. Building on screening with the Edmonton Symptom Assessment System (ESAS), e-PROMs were triggered based on cut scores to focus multidimensional assessment and management of pain (BPI), fatigue (CFS), anxiety (GAD-7) and depression (PHQ-9). Methods: Multifaceted implementation strategies and practice change coaching facilitated the use of e-PROMs to improve symptom outcomes. A mixed-method, pre-post quasi-experimental design assessed process and impact of the intervention on symptom screening rates, symptom burden, patient experience and activation, clinician satisfaction, team collaboration and health care use. Mann-Whitney U statistics examined significance of change from baseline to the 8-month post comparison. Qualitative data explored uptake of e-PROMs in practice. Results: Over the implementation period 10,248 ESAS screens were completed in iPEHOC clinics; 17.5% triggered an additional e-PROM. A slight improvement was noted in person-centeredness of communication (mean change of 1.43 to 1.37; four-point scale of 1 = very satisfied, 4 = very dissatisfied) and in team collaboration. A significant increase in patient activation levels (p = 0.045) was related to decreased emergency department visits (2% pre/post change, p = 0.81) and hospitalization within 30 days of an e-PROMs completion (2.2% change, p = 0.034) in Ontario. Patients and clinicians perceived e-PROMs as valuable to focus communication in the clinic visit and for shared treatment planning. Focus group data suggests that patients use e-PROMs as a ‘self-check-in’, to communicate their symptoms and normalize disclosure of depression in clinical care. Conclusions: Uptake of e-PROMs in diverse settings is complex and demanding. Improving symptom management quality requires PROM data to be fed-back for ‘real-time’ use in the clinical encounter and practice change facilitation for meaningful use in routine care.