tbuckley/cabot-search huggingface dataset:
Bioresorbable Scaffolds versus Metallic Stents in Routine PCI
Authors: Joanna J. Wykrzykowska, Robin P. Kraak, Sjoerd H. Hofma, Rene J. van der Schaaf, E. Karin Arkenbout, Alexander J. IJsselmuiden, Joëlle Elias, Ivo M. van Dongen, Ruben Y.G. Tijssen, Karel T. Koch, Jan Baan, M. Marije Vis, Robbert J. de Winter, Jan J. Piek, Jan G.P. Tijssen, Jose P.S. Henriques
Journal: New England Journal of Medicine (2017)

Bioresorbable vascular scaffolds were developed to overcome the shortcomings of drug-eluting stents in percutaneous coronary intervention (PCI). We performed an investigator-initiated, randomized trial to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent in the context of routine clinical practice.We randomly assigned 1845 patients undergoing PCI to receive either a bioresorbable vascular scaffold (924 patients) or a metallic stent (921 patients). The primary end point was target-vessel failure (a composite of cardiac death, target-vessel myocardial infarction, or target-vessel revascularization). The data and safety monitoring board recommended early reporting of the study results because of safety concerns. This report provides descriptive information on end-point events.The median follow-up was 707 days. Target-vessel failure occurred in 105 patients in the scaffold group and in 94 patients in the stent group (2-year cumulative event rates, 11.7% and 10.7%, respectively; hazard ratio, 1.12; 95% confidence interval [CI], 0.85 to 1.48; P=0.43); event rates were based on Kaplan-Meier estimates in time-to-event analyses. Cardiac death occurred in 18 patients in the scaffold group and in 23 patients in the stent group (2-year cumulative event rates, 2.0% and 2.7%, respectively), target-vessel myocardial infarction occurred in 48 patients in the scaffold group and in 30 patients in the stent group (2-year cumulative event rates, 5.5% and 3.2%), and target-vessel revascularization occurred in 76 patients in the scaffold group and in 65 patients in the stent group (2-year cumulative event rates, 8.7% and 7.5%). Definite or probable device thrombosis occurred in 31 patients in the scaffold group as compared with 8 patients in the stent group (2-year cumulative event rates, 3.5% vs. 0.9%; hazard ratio, 3.87; 95% CI, 1.78 to 8.42; P<0.001).In this preliminary report of a trial involving patients undergoing PCI, there was no significant difference in the rate of target-vessel failure between the patients who received a bioresorbable scaffold and the patients who received a metallic stent. The bioresorbable scaffold was associated with a higher incidence of device thrombosis than the metallic stent through 2 years of follow-up. (Funded by Abbott Vascular; AIDA ClinicalTrials.gov number, NCT01858077 .).
Phase I clinical trial of lenalidomide with temsirolimus in patients with advanced cancer.
Authors: Prasanth Ganesan, Sarina Anne Piha-Paul, Aung Naing, Gerald Steven Falchook, Jennifer J. Wheler, Filip Janku, Ralph Zinner, Shell Laday, Merrill S. Kies, Apostolia Maria Tsimberidou
Journal: Journal of Clinical Oncology (2013)

2604 Background: Lenalidomide (immunomodulatory and antiangiogenic drug) and temsirolimus (mTOR inhibitor) are potentially synergistic (Raje N, Blood 2004;104(13):4188). We conducted a phase I study of the combination in patients with advanced cancers. Methods: During the escalation phase, lenalidomide (PO days 1-21) and temsirolimus (IV, Q weekly) were given at the following respective doses: level 1 (10 mg, 15mg); level 2 (10 mg, 20 mg); level 3 (20 mg, 20 mg); and level 4 (20 mg, 25 mg) (1 cycle = 28 days). A “3+3” study design was used. The maximum tolerated dose, dose-limiting toxicity, and response were assessed. Results: Forty- three patients were treated (median age: 58 (21-80) years; male/female: 26:17). The most common diagnoses were colorectal cancer (N=5), sarcoma (N=5) and adenoid cystic carcinoma (N=4). Overall, 121 cycles (median: 2) were administered. No dose limiting toxicities were observed. The maximum tested dose (level 4) was used for expansion. Grade 3-4 toxicity (all reversible) occurred in 19 (44%) patients: neutropenia (N=12), thrombocytopenia (N=6), and infection (N=1). Of 43 patients, 31 (72%) received anticoagulation prophylaxis. There were no thrombotic events. Of 36 patients who were evaluable for response, PR was noted in 1 (2.7%), and stable disease (SD) was noted in 17 (47%) patients (SD ≥6 months: 17%). Tumors with SD≥6 months were soft tissue sarcoma, 2/5 (40%), adenoid cystic carcinoma, 1/4 (25%), parotid ca, 1/2 (50%), adrenocortical ca 1/3 (33%), and neuroendocrine ca, 1/4 (25%) (Table). The median progression-free survival was 2.2 months (95% CI, 1.5-2.9) and overall survival was 7.8 months (95% CI, 5.1-10.6). Conclusions: Lenalidomide and temsirolimus combination was well tolerated and had antitumor activity in selected participants with advanced cancer. Clinical trial information: NCT01183663. [Table: see text]
Identification of germline mutations in men with early onset prostate cancer.
Authors: Patrick Pilie, Anna M. Johnson, Kimberly A. Zuhlke, Linda A. Okoth, Scott Tomlins, Kathleen A. Cooney
Journal: Journal of Clinical Oncology (2015)

5045 Background: Prostate cancer (PCa) is generally considered a disease of older men, however, approximately 10% of new diagnoses occur in young men ( < 56 years) and some of these cases are clinically aggressive. Epidemiological evidence suggests that early age of cancer onset is associated with increased genetic susceptibility. Methods: For this pilot study, we employed a gene panel approach to identify germline mutations in cancer-associated genes among men diagnosed with early-onset (EO) PCa. Fifty-five men with PCa diagnosed before age 56 were selected from the University of Michigan (UM) Prostate Cancer Genetics Project, a large family-based study of familial and EO PCa. Each of the men also had at least one of the following characteristics: 1) family history of breast and/or ovarian cancer, 2) multiple primary cancers in addition to PCa, and/or 3) clinically aggressive PCa defined as death from disease before age 66 and/or diagnosis of metastatic disease before age 56. All patients provided written consent and this project was approved by the UM IRBMED. Germline DNA from the 55 men was sequenced using the GeneRead Human Comprehensive Cancer Panel (Qiagen) which includes 124 genes previously associated with a variety of cancers. Potentially deleterious variants were confirmed via Sanger sequencing and then tested in all family members with DNA available to assess co-segregation with PCa status. Results: Over 2500 germline variants were identified, including 349 missense, 4 nonsense, and 6 frameshift variants. Seven of the ten protein truncating variants were confirmed. The 7 true positives included nonsense variants in MSH2, ATM, and KRAS, as well as frameshift variants in FGFR3, TET2, and BRCA2. Conclusions: Overall, 7 of 55 (~13%) high selected EO PCa cases harbored protein-truncating variants in one of the genes examined. Although deleterious mutations in BRCA2 and MSH2 have previously been associated with PCa risk, the other genes have been less well-studied for their role in PCa susceptibility. Further studies of this unique patient population will likely uncover additional novel variants and genes linked with PCa risk which may provide new insights into the development of the disease and ultimately suggest new therapeutic targets.
Multiplex testing of driver mutations in non-small cell lung cancer (NSCLCs) of African-American (AA) patients.
Authors: Shirish M. Gadgeel, Michele L Cote, Ann G. Schwartz, Aliccia Bollig-Fischer, Susan Land, Angie Wenzlaff, Wei Chen, Antoinette J. Wozniak, Ammar Sukari, Laura Mantha, Gerold Bepler
Journal: Journal of Clinical Oncology (2013)

7561 Background: Recently driver genetic alterations have been identified in NSCLC that can be targeted for therapeutic interventions. Previous reports have suggested that rates of certain mutations may vary according to ethnic background. We conducted multiplex testing of NSCLCs of AA and white patients to assess variability in the mutation rates by race. Methods: We identified tumor tissues of 136 AA and 320 white NSCLC patients collected as part of three different institutional review board approved studies. Using the Sequenom MassArray system and a multiplexed panel, we analyzed tumor DNA for 214 oncogenic mutations in 26 genes previously identified in NSCLC. Estimated risk (Odds Ratios (OR)) of any mutation and specific gene mutations among AA patients compared to white patients were calculated after adjusting for age, sex, smoking status and histology (adenocarcinoma versus non-adenocarcinoma). Information on smoking status was unavailable on 46 patients and was not included in calculations of ORs for some genes (OR ª ). Results: The median age at diagnosis was 60 vs 66 years in AA vs white patients; 43% of AA patients and 66% of white patients were males; 69% of AA patients and 52% of white patients had adenocarcinoma; 66% of AA patients and 85% of white patients had stage I/II NSCLC and 10% of AA patients and 6% of white patients were never smokers. 43% of the AA patients and 47% of white patients had at least one mutation detected (OR = 0.78; 0.5-1.2). 19% of AA patients and 6% of white patients had more than 1 mutation detected (OR 2.3; 1.1-4.9). AA patients were more likely to harbor mutations in STK11 (LKB1) (OR=8.4; 3.2-21.8) and NOTCH1 (OR ª =8.1; 2.2-30.8), and they were less likely to have MET mutations (OR ª = 0.12; 0.02-0.9) then white patients. While not statistically significant, AA had lower prevalence of Kras mutations (OR=0.64, 0.3-1.4) and p53 mutations (OR= 0.82; 0.4-1.6). Conclusions: Our analysis of NSCLCs shows that AAs were more likely to have multiple genetic mutations than whites and the mutation profile differs by race.
A randomized double-blind phase III trial comparing vintafolide plus pegylated liposomal doxorubicin (PLD) versus PLD plus placebo in patients with platinum-resistant ovarian cancer (PROCEED).
Authors: R. Wendel Naumann, Lucy Gilbert, Anthonette M. Miller, Hong Ma, Sharad A. Ghamande, Ignace Vergote
Journal: Journal of Clinical Oncology (2013)

TPS5613 Background: Folate receptor (FR) is expressed on the majority of epithelial ovarian cancers and FR expression appears to be a negative prognostic factor in this setting. Vintafolide (EC145) is a folate-conjugate designed to selectively deliver desacetylvinblastine monohydrazide (DAVLBH) to FR-expressing cells. 99m Tc-Etarfolatide (EC20) is a technetium-labeled folate that identifies FR-expressing tumors. In a phase 2 study comparing vintafolide + PLD with PLD alone, the combination demonstrated a statistically and clinically significant delay in PFS (5.0 months) compared with PLD alone (2.7 months) in women with platinum-resistant ovarian cancer (Naumann et al, ASCO 2011). Data also indicated that 99m Tc-etarfolatide may have utility for selecting patients most likely to benefit from vintafolide therapy. Methods: This is an international, randomized, double-blind, placebo-controlled phase 3 study of PLD ± vintafolide therapy compared in patients with primary or secondary platinum-resistant ovarian cancer (NCT01170650). Key eligibility criteria include: ≥18 years, pathology-confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma, prior platinum-based chemotherapy, a RECIST v1.1 measureable lesion, and ECOG performance status 0 or 1. At baseline, patients undergo 99m Tc-Etarfolatide imaging to identify FR-positive lesions and are subsequently randomized to the vintafolide ± PLD. PLD (50 mg/m 2 ) adjusted for Ideal Body weight is administered on day 1 of a 4-week cycle and treatment continues until the maximum allowable cumulative dose (550 mg/m 2 ) is reached or until disease progression or intolerable toxicity. Vintafolide (2.5 mg) or placebo is administered on days 1, 3, 5, 15, 17, and 19 of a 4-week cycle and treatment can continue for up to 20 cycles or until unacceptable toxicity or disease progression. The primary objective is to assess PFS based on investigator assessment (RECIST v1.1) in FR positive patients. Secondary objectives include OS, safety/tolerability, overall response rate, and disease control rate. Enrollment to the study is currently ongoing. Clinical trial information: NCT01170650.
Impact of cetuximab on chemoradiation use in older patients with locally advanced head and neck cancer.
Authors: Shrujal S. Baxi, Eric Jeffrey Sherman, Coral L Atoria, Nancy Y. Lee, David G. Pfister, Elena B. Elkin
Journal: Journal of Clinical Oncology (2013)

6594 Background: The benefit of chemoradiation (CTRT) in the treatment of locally advanced head and neck cancer (LAHNC) declines in older and sicker patients. In 2006, the FDA approved cetuximab in LAHNC. Cetuximab with radiation has a perceived lower side effect profile compared to standard chemotherapies used in CTRT. Our objective was to examine the impact of cetuximab on the use of CTRT in elderly patients with LAHNC. Methods: We identified adults aged 66 and older diagnosed with LAHNC between 1999 and 2007 in the Surveillance Epidemiology and End Results (SEER)-Medicare linked database. Treatment was categorized as CTRT or other based on Medicare claims within 6 months of diagnosis. We excluded patients who did not receive definitive treatment. In patients who had CTRT, we identified use of cetuximab based on drug-specific billing codes. We assessed trends in the use of CTRT over the entire study period and in the use of cetuximab since 2006. We examined the influence of age and comorbidity on the likelihood of receiving CTRT before and after 2006 adjusting for clinical and demographic factors. Results: We identified 4,809 patients with LAHNC. One-fourth were ≥80 years and almost a fifth had a Charlson comorbidity score (CCS) of ≥2. Overall more than 20% of patients received CTRT. The use of CTRT more than tripled over time, from 10% of patients diagnosed in 1999 to 38% in 2007 (p&lt;0.0001 for trend). Of the 336 patients who had CTRT since 2006, 45% received cetuximab. Prior to 2006, patients ≥80 years or those with a CCS of ≥2 were significantly less likely to be treated with CTRT compared to younger patients or those with a CCS of 0. In patients diagnosed in 2006 or later, age and comorbidity no longer predicted the likelihood of receiving CTRT. Conclusions: In this population-based cohort of older adults, the use of CTRT increased substantially over time. The availability of cetuximab, with a perceived gentler side effect profile, may have increased the use of CTRT, especially in older and sicker patients. [Table: see text]
Outcome of elderly DLBCL patients with 6xCHOP-14 and 8 rituximab (R) applications given over an extended period (SMARTE-R-CHOP-14 trial of the DSHNHL).
Authors: Niels Murawski, Gerhard Held, Samira Zeynalova, Carsten Mueller, Viola Poeschel, Andreas Viardot, Mathias Haenel, Ulrich Keller, Marcel Reiser, Marita Ziepert, Norbert Schmitz, Michael Pfreundschuh
Journal: Journal of Clinical Oncology (2012)

8025 Background: 6xCHOP-14 with 8xR given over an extended period improved 3-year EFS (67% vs. 54%; p=0.030) and OS (80% vs. 67%, p=0.034) of poor-prognosis patients (IPI=3-5) in the SMARTE-R trial compared to the RICOVER-60 trial where patients received 8xR every 2 weeks. Because we had recently shown (Mueller et al., Blood 2012) that elderly male patients have a faster R clearance (12.68 ml/h vs. 8.21 ml/h; p=0.003) and shorter serum elimination half life (t 1/2ß =24.7 vs. t 1/2ß =30.7 days; p=0.003) than females, we analyzed whether these differences translated into different outcomes by comparing the results achieved by elderly female and male patients in the RICOVER-60 and SMARTE-R trials. Methods: In SMARTE-R, 189 evaluable elderly (61-80 y) pts. with DLBCL received 6 cycles of 2-weekly CHOP-14 combined with 8xR on days -4, -1, 10, 29, 57, 99, 155, and 239. The primary endpoint was event-free survival (EFS). 306 pts treated within the RICOVER-60 trial with 6xCHOP-14 + 8 R given on days 1, 15, 29, 43, 57, 71, 85 and 99 served as controls. Results: The 3-year EFS of 51 poor-prognosis male patients in SMARTE-R was 67% compared to 47% of 66 poor-prognosis male patients treated in RICOVER-60 (p=0.037); the respective figures were 71% vs. 53% (p=0.051) for PFS and 80% vs. 60% (p=0.027) for OS. In contrast, female poor-risk patients had only a small benefit from the extended rituximab exposure in SMARTE-R (n=48) compared to RICOVER-60 (n=57): 67% vs. 61% (p=0.354) for EFS; 71% vs. 67% (p=0.489) for PFS; and 80% vs. 76% (p=0.528) for OS. Conclusions: Elderly male patients with poor-prognosis DLBCL who have a faster R clearance and shorter R serum elimination half life than female patients, benefit significantly from the longer R exposure in SMARTE-R with a gain of 20% in 3-year OS, while the outcome of female patients was only slightly improved. Even though R maintenance has failed to demonstrate any benefit in the primary treatment of DLBCL to date, these results underline the importance of a minimum exposure time of R in order to exploit its full therapeutic potential in DLBCL. Supported by Deutsche Krebshilfe.
Priorities for Public Health Spending
Authors: Sean Cahill, Kenneth Mayer, Stephen Boswell
Journal: JAMA (2017)

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Caregivers’ perception of advanced cancer patients’ quality of death: Impact on caregiver suicidal ideation in bereavement.
Authors: Caroline H Abbott, Holly Gwen Prigerson, Paul K Maciejewski
Journal: Journal of Clinical Oncology (2013)

9522 Background: Evidence suggests that patients’ quality of life (QOL) at the end of life (EOL), i.e., patients’ quality of death, may affect the health and well-being of informal family caregivers. Here we examine the relationship between family caregivers’ perception of patients’ QOL at the EOL and caregiver suicidal ideation in bereavement. Methods: Our analysis was based on data from a sub-sample of family caregivers (N=112) from the Coping with Cancer Study, an NCI-funded multicenter prospective cohort investigation of advanced cancer patients and their caregivers enrolled September 2002 – February 2008. Caregiver baseline suicidal ideation was assessed using the Yale Evaluation of Suicidality (YES) Scale a median of 4.1 months pre-loss; caregivers’ perception of patients’ overall distress in the last week of life was assessed a median of 1.9 months post-loss; and caregiver suicidal ideation in bereavement was assessed using the YES a median of 6.5 months post-loss. Suicidal ideation was defined as a positive screen on the YES. Multiple logistic regression analysis examined the effect of caregivers’ perception of patients’ quality of death on bereaved caregiver suicidal ideation, adjusting for caregivers’ baseline suicidal ideation and potential demographic confounds. Results: Caregivers’ perception of patients’ overall distress at the EOL was significantly related to caregivers’ suicidal ideation post-loss (AOR=1.26, p=0.022) adjusting for caregivers’ baseline suicidal ideation, relationship to patient, and years of education. Conclusions: The more caregivers’ perceive their loved ones’ quality of death to be poor, the more they are at risk for suicidal ideation in bereavement. Improving QOL at the EOL will not only benefit patients but also protect caregivers from suicidal ideation.
Ovarian metastasis from midgut neuroendocrine tumors: Incidence, clinical implications, and management options—An update.
Authors: Aman Chauhan, Lowell Brian Anthony, David T Beyer, Yi-Zarn Wang
Journal: Journal of Clinical Oncology (2017)

446 Background: Midgut neuroendocrine tumors (NETs) are rare malignancies that can produce carcinoid syndrome and/or carcinoid heart disease. The incidence of ovarian metastasis, their clinical implications, and the optimal management strategy for these metastasis have not been well studied. We hypothesized that patients with ovarian metastasis will have a high incidence of carcinoid syndrome and carcinoid heart disease. Methods: Charts of 431 female patients seen in our NET clinic between October 2006 and December 2014 with a diagnosis of midgut NET were reviewed. Patients who had a previous bilateral oophorectomy with or without total abdominal hysterectomy were excluded. The incidence of ovarian metastasis, carcinoid syndrome and carcinoid heart disease was calculated. Median survival and 5-year survival rates were determined via the Kaplan-Meier Method. Results: Forty-one (41/431, 10%) patients were found to have ovarian metastasis. Twenty-four (24/41, 59%) patients exhibited carcinoid syndrome and three (3/24, 13%) patients with carcinoid syndrome developed carcinoid-related heart disease. 5-year survival rates for the patients with and without ovarian metastasis were 92% and 87%, respectively. Conclusions: Ovarian metastasis was found in 10% patients with metastatic midgut NET. Fifty-nine percent of these patients exhibited carcinoid syndrome and thirteen percent of which developed carcinoid heart disease, in spite of aggressive somatostatin analog therapy. To improve quality of life, routine therapeutic or prophylactic oophorectomy is recommended for female patients undergoing cytoreductive surgery for their midgut NET, especially for those who are peri- or post-menopausal.