tbuckley/cabot-search huggingface dataset:
P05.46 Metachronous malignancies and brain tumor in children with germline TP53 mutation
Authors: M Guidi, L Giunti, A Buccoliero, S Farina, C Fonte, C Caporalini, C Moscheo, M Censullo, L Genitori, I Sardi
Journal: Neuro-Oncology (2018)

Somatic TP53 mutations have been reported to occur in almost every type of cancer. They are common alterations in brain tumors. Nevertheless, germline mutations of TP53 gene are linked to Li-Fraumeni syndrome (LFS), a tumor susceptibility condition, characterized by an increased risk of developing early synchronous or metachronous malignancies. TP53 germline mutations have also been reported in individuals with no family history or with a family history not fulfilling LFS characteristics. We retrospectively considered 7 patients with brain tumors followed at the Neuro-Oncology Unit between September 2008 and January 2018. The median age at diagnosis was 13,7 years (range 1–31); Six patients were male and one female. Five patients developed metachronous tumors. Two LFS patients had only a primary anaplastic astrocytoma. Five (71,4%) patients had primary brain tumor (3 anaplastic astrocytoma, 1 ependymoma, 1 medulloepithelioma). Molecular analysis of TP53 gene was performed in all patients. Family’s cancer history was investigated. Six patients (85,7%) had a germline TP53 mutation all contained between exons 4 and 7. Only one patient with metachronous tumors (leukemia and ependymoma) and without a family’s cancer history did not show a TP53 mutation. Two patients (28,6%) were negative for family’s cancer history but positive for germline TP53 mutation, ones with history of primary medulloepithelioma and osteosarcoma. The second patient had two brain tumors (anaplastic astrocytoma and PNET). The second tumors developed after two years from the first diagnosis. One LFS patient positive for germline TP53 mutation died for an anaplastic astrocytoma. The other four patients (57,1%) resulted positive both for germline TP53 mutation and for family’s cancer history. The median time between the first and second diagnosis was 7,2 years. Germline TP53 mutation predisposes to develop synchronous or methachronous tumors even after many years. Our study evidenced that germline TP53 mutation is also frequent in brain tumor patients without cancer family’s history. Therefore they must necessarily be constantly monitored with a correct follow-up and the decisions to be made to avoid unnecessary therapy when they have a poor outcome.
Accuracy of <sup>68</sup>Ga-PSMA11 PET/CT on recurrent prostate cancer: Preliminary results from a phase 2/3 prospective trial.
Authors: Wolfgang Fendler, Jeremie Calais, Jeannine Gartmann, Nicholas George Nickols, Robert Evan Reiter, Matthew Rettig, Thomas A Hope, Roger Slavik, Pawan Gupta, Andrew Quon, Martin Allen-Auerbach, Ken Herrmann, Johannes Czernin, Matthias Eiber
Journal: Journal of Clinical Oncology (2018)

5001 Background: 68Ga-PSMA11 PET/CT provides improved localization of biochemically recurrent prostate cancer. For approval and reimbursement, accuracy needs to be established in a prospective study employing independent lesion validation. Methods: In this phase 2/3 prospective trial (NCT02940262), patients with biochemically recurrent prostate cancer after primary prostatectomy (n = 205) or radiation therapy (n = 45) underwent 68Ga-PSMA11 PET/CT. Presence of prostate cancer was recorded on a patient and region base. Regions were prostate bed, pelvis, extra-pelvic, and bone. Lesions were validated in 51% of PET/CT-positive patients by histopathology (n = 33), imaging (n = 62) and/or PSA after targeted radiation therapy (n = 9 patients). PSA response after 68Ga-PSMA11 PET/CT guided focal salvage therapy (surgery/radiotherapy) was recorded in 23 of 25 patients (8% drop out). Endpoints were positive predictive value (PPV), detection rate and outcome. Results: PPV validated by histopathology was 85% on a patient base (primary endpoint). PPV as determined by any type of validation was 89% on a patient and 91% on a region base. 68Ga-PSMA11 PET/CT localized recurrent prostate cancer in 197 of 250 (79%) patients; stratified by PSA: 41% for < 0.5 ng/ml (n = 54), 66% for 0.5 to < 1.0 ng/ml (n = 38), 86% for 1.0 to < 2.0 ng/ml (n = 36), 96% for 2.0 to < 5.0 ng/ml (n = 55), and 99% for ≥5.0 ng/ml (n = 67). Lesion location was in 35% prostate bed, 61% pelvis, 35% extra-pelvic, and 31% bone. Following focal salvage therapy alone, 18 (78%) patients had a PSA drop of 50% or more, 7 (30%) patients had biochemical complete response (PSA undetectable). Conclusions: Using an independent reference standard, we establish high 68Ga-PSMA11 PET/CT PPV for localization of recurrent prostate cancer. PET/CT guided salvage therapy resulted in high biochemical response rates. Pooled multicenter findings will be submitted for a New Drug Application. Clinical trial information: NCT02940262.
Post resection circulating residual disease monitoring in early stage lung and colorectal cancer patients using a circulating cell-free DNA assay with ultra-high accuracy and specificity.
Authors: Annie Maslan, Ariel Jaimovich, Narsi Rajagopalan, Michelle Tan, Stefanie Mortimer, Darya Chudova, Drew Kennedy, Hee Cheol Kim, Seung Tae Kim, Se-Hoon Lee, Jeeyun Lee, Helmy Eltoukhy, Jhingook Kim, AmirAli Talasaz
Journal: Journal of Clinical Oncology (2017)

e23068 Background: Analysis of cell-free circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) is a promising method for detecting and monitoring earlier stage cancers. Liquid biopsies have a large potential to detect cancer earlier upon initial recurrence and to aid in adjuvant decision making through a non-invasive and highly accurate mechanism. Methods: We developed a 30kb ctDNA capture panel based on the landscape of genomic alterations in ctDNA of over 10,000 advanced cancer patients with high theoretical clinical sensitivity for colorectal (96%) and lung (87-93%) cancers. The panel was validated with high analytical PPV (86% at MAFs &lt; 0.025%, 96% at MAFs &gt; 0.025%). We applied the panel to a clinical study of 63 healthy donors and also 40 early stage (II/III) CRC and lung cancer patients with both pre- and post-tumor resection blood draws. Tumor samples were also collected at the time of the surgical resection. Results: Overall, the detection rate of ctDNA in pre-op blood draws was 72% (13/18) in CRC and 67% (12/18) in lung cancer patients. In the post-op blood draws ctDNA was detectable in 11% (2/18) of CRC and 11% (2/18) of lung cancer cases. For lung cancer patients, the median MAF in pre-op was 0.06% (0.01%-8.47%, n = 51) and in post-op was 0.06% (0.02%-4.14%, n = 38). For CRC patients, the median MAF in pre-op was 0.18% (0.01%-9.26%, n = 51) and in post-op was 0.36% (0.04%-9.5%, n = 18). Sixty-three healthy donor plasma samples were screened at similar cfDNA input amounts and nine (14%) had mutations; the majority of the mutations were also detected in matched leukocyte DNA. To assess a clinically relevant biological false positive background rate in lung cancer patients, screening of cancer-free smokers is ongoing. Conclusions: We have developed a highly sensitive and specific universal assay for the detection of ctDNA in early stage CRC and lung cancer patients without the requirement of a priori knowledge of tumor mutations. This technology allows for a promising non-invasive route for molecular monitoring of residual disease post-surgery and for early detection of relapse compared to traditional methodologies.
Early clinical results of a phase II trial evaluating neoadjuvant chemotherapy followed by chemoradiation and maintenance gefitinib in locally advanced cervical cancer.
Authors: Rony Benson, Sushmita Pathy, Lalit Kumar, Sandeep Mathur, Rabindra Pandey, Subhash Chander, Vatsla Dadhwal, BK Mohanti
Journal: Journal of Clinical Oncology (2016)

e17014 Background: Neoadjuvant chemotherapy (NACT) followed by chemoradiation (CTRT) is hypothesized to improve survival in locally advanced cervical cancer (LACC) by reducing distant metastasis. Implication of epithelial growth factor receptor (EGFR) expression and maintenance gefitinib in cervical cancer has not been addressed. The study was aimed to evaluate NACT followed by CTRT and maintenance gefitinib in LACC. Methods: This was a phase II single arm study. 25 patients (pts) of LACC were enrolled between July 2012 and May 2013. All patients received 6 weekly doses of Paclitaxel (60mg/m-2) and Carboplatin (AUC 2), followed by CTRT (external beam radiotherapy 50.4Gy/28fractions/5.5 weeks with concurrent Cisplatin 40 mg/m2) and brachytherapy (7 GyX3 weekly fraction). EGFR expression was evaluated by immunohistochemistry. Maintenance gefitinib was advised for 1 year. Toxicity was graded according to the common terminology criteria for adverse events version 4.0. The study was approved by the institute ethics committee. Results: 25 patients of LACC were enrolled with median age 47 years (range 32 - 60). 14 patients stage were IIIB and 11 patients belonged to stage IIB. 24 pts completed the NACT and CTRT and were started on gefitinib maintenance therapy. 20 patients completed intended the treatment . Median follow up was 27 months (range 4-37). Response rate [partial and complete] to NACT and CTRT was 96 %.EGFR was moderately or strongly expressed in 86.3 % of the pts. Age, hemoglobin, lymph node, and tumor size had no statistically significant association with treatment outcome. 12 pts (50%) developed grade ≥ II diarrhea, 3(12%) developed ≥ III diarrhea needing treatment break. Grade II skin reaction was observed in ten patients (41.6%). No significant correlation was demonstrated between the expression of EGFR and response to treatment. 64% of patients were in complete remission at the last follow up. Conclusions: NACT followed by CTRT is associated with high initial response rate in LACC. Gefitinib as maintenance therapy is well tolerated.
TCT-787 High-Sensitive Cardiac Troponin Predicts 2-years Mortality in Patients with Coronary Artery Disease- subanalysis of the GLOBAL LEADERS trial
Authors: Chun Chin Chang, Ply Chichareon, Norihiro Kogame, Rodrigo Modolo, Kuniaki Takahashi, Angel Cequier, Didier Carrie, Rod Stables, Kees-Jan Royaards, Jürgen vom Dahl, Yoshinobu Onuma, Christian Hamm, Pascal Vranckx, Marco Valgimigli, Stephan Windecker, Patrick Serruys
Journal: Journal of the American College of Cardiology (2018)
Comparison of characteristics and outcomes of lung cancer in African American females and Non African American females.
Authors: Shyam Ravisankar, Michael Szpejda, Lauren Elreda, Alice Joy Cohen
Journal: Journal of Clinical Oncology (2018)

e18647 Background: There are limited studies of lung cancer treatment which include African American females (AAF) and specifically look at their outcomes. Our study aims to assess and determine any differences in characteristics of lung cancer between AAF and Non-African American Females (NAAF) treated in a single institution. Methods: We reviewed archival medical records of AAF and NAAF diagnosed with lung cancer between 2010 and 2015 treated at Newark Beth Israel Medical Center (NBI). Patients where identified from the cancer registry and characteristics were extracted from medical records. Female patients older than eighteen years with a diagnosis of primary lung cancer of any histology were included. Patient survival and age at diagnosis of the two groups were compared using T-Tests. Presence of brain metastases, smoking history and cancer stage at diagnosis were compared using Chi square tests. Results: We included 137 AAF and 34 NAAF. Overall survival was similar between AAF and NAAF (median 11 months vs. 11.5 months p = 0.24). The age at diagnosis was also similar (median of 66 years vs 65.5 years p = 0.68). AAF had a higher proportion of smokers (31.5% vs. 14.7% p < 0.05) and a higher proportion had stage 4 disease at diagnosis (52.8% vs. 38.2% p < 0.05). The distribution of cancer histology (Small Cell Carcinoma 6.3% vs. 8.8%, Non-Small Cell Cancers 93.7% vs. 91.2%) was similar. The most common histology was adenocarcinoma 40.2% for AAF and 44.1% for NAAF. The presence of brain metastasis was not significantly different between AAF and NAAF ( 11% vs. 8.8% p = 0.93). Treatment differences for AAF and NAAF were as follows: primary surgery 9.5% vs. 26.5%, chemotherapy 13.4% vs. 5.9%, combined chemotherapy & radiation 30.7% vs. 17.7%). Conclusions: AAF and NAAF with lung cancer treated in our hospital have similar outcomes. The higher incidence of smoking and metastatic disease at presentation in AAF may indicate the need for increased smoking cessation education and referral to lung cancer screening programs in this population. Some treatment differences were noted but were attributed to more advanced disease presentation in AAF.
Factors predicting the use of immunotherapy for patients with advanced melanoma.
Authors: Richard Wayne Joseph, Alicia Shillington, Cynthia Macahilig, Scott J. Diede, Vaidehi Dave, Qing Harshaw, Frank Xiaoqing Liu
Journal: Journal of Clinical Oncology (2018)

9571 Background: Both pembrolizumab (PEMBRO) and the combination of ipilimumab and nivolumab (IPI+NIVO) are approved by the US FDA for treatment of advanced (unresectable or metastatic) melanoma. Clinical trials have demonstrated different benefit-risk profiles associated with each that may impact selection in the real-world. We performed a retrospective chart review of patients with advanced melanoma to understand patient characteristics associated with PEMBRO vs IPI+NIVO treatment selection. Methods: A retrospective, chart-review study was conducted in the US; 12 oncologists from 12 US academic centers and affiliated satellite clinics were recruited to contribute patients ≥18 years of age with advanced melanoma receiving PEMBRO or IPI+NIVO in any line between Jan 1, 2016 – Dec 30, 2017. Demographics and baseline disease characteristics were compared between cohorts in univariate analysis. A mixed-effects logistic regression model with site of treatment specified as a random effect was created to predict PEMBRO vs IPI+NIVO selection using parameters identified in univariate analysis. Results: 400 patients were included, 200 each PEMBRO and IPI+NIVO. There were no significant differences in mean age, race, gender, family income, education level, insurance status, comorbidity index, site of metastasis, and line of therapy between the cohorts. However, the PEMBRO cohort had poorer Eastern Cooperative Group (ECOG) status at treatment start 70.5% ECOG 0 or 1 vs 88.0% (p < 0.001), were more likely to be PD-L1 positive (76.9% vs 63.1%, p = 0.011), and less likely to harbor a BRAF mutation (34.8% vs 49.7%, p = 0.003). In regression, PEMBRO was favored over IPI-NIVO in ECOG 2-3 patients vs 0-1 (OR 6.6, 95%CI 3.0, 14.7), and PD-L1 expression positive (OR 4.5, 95%CI 1.9, 10.4). Those with BRAF wild-type were more likely to receive PEMBRO (OR 2.2, 95%CI 1.4, 3.6) than IPI+NIVO. Conclusions: In the real-world, patient factors are significantly associated with treatment selection in advanced melanoma. PEMBRO appears to be selected more often than IPI+NIVO in patients with poorer ECOG performance status, PD-L1 positive tumors, BRAF wild-type tumors. Any real-world comparison of outcomes between treatments should take this into consideration.
The value of Fn14, CD44v, and EGFR expression in lung adenocarcinoma patients with and without activating EGFR gene mutation.
Authors: Maciej Bryl, Katarzyna Bednarek-Rajewska, Przemysław Zalewski, Małgorzata Janicka-Jedyńska, Rodryg Ramlau, Aleksander Barinow Wojewódzki, Aldona Woźniak
Journal: Journal of Clinical Oncology (2017)

e20514 Background: Lung cancer is considered the most common cause of death in the world. The prognosis for patients is poor and depends on the clinical stage and the histological type of cancer. There is a need to identify and develop new therapeutic targets that could improve the prognosis of NSCLC patients and may be responsible for development of resistance to TKI therapy. Increased expression of Fn14 or CD44v and EGFR was observed in many tumors and also correlated with the overall survival of NSCLC patients Methods: We analyzed the clinical data and the immunohistochemical expression of Fn14, CD44v and EGFR in tumor tissues from 61 patients with NSCLC divided in two groups according to the presence of activating EGFR gene mutation. The aim of the study was to evaluate the correlation between the expression of the studied molecules and the neoplastic disease course of NSCLC patients. Results: Increased expression of Fn14 was observed in study group (B) compared to expression of this molecule in the control group (K). There were no differences in the intensity of the reaction with anti CD44v and EGFR antibodies in both groups. OS was significantly longer in the study group. Histological grade of tumor correlated with the intensity of CD44v expression in both groups. There was no correlation between the OS and Fn14 expression in any group. Negative correlation was noted between the expression of CD44v and the OS in the study group and between EGFR expression and the OS in both groups. Conclusions: Our observations suggest that the expression of CD44v and EGFR may be useful clinical markers of prognostic value in lung adenocarcinoma patients regardless of the presence of activating mutation in EGFR gene. Simultaneous assessment of Cd44v and EGFR expression may grant a greater prognostic value than the assessment of each receptor separately. Increased expression of Fn14 receptor in patients with EGFR gene mutation may become a new target in therapy allowing to eliminate the problem of secondary resistance to treatment with TKI’s
TCT-586 Long-term performance of the Dual-therapy COMBO stent: results from the REMEDEE Registry
Authors: Laura Kerkmeijer, Deborah Kalkman, Pier Woudstra, Peter Den Heijer, Ian Brian Alexander Menown, Harry Suryapranata, Andrejs Erglis, Karin Arkenbout, Andres Iñiguez, Jan Tijssen, M. Beijk, Robert de Winter
Journal: Journal of the American College of Cardiology (2018)
Cardiovascular disease and preventive care among cancer survivors: A population-based study.
Authors: Kevin A. Pearlstein, Ramsankar Basak, Ronald C. Chen
Journal: Journal of Clinical Oncology (2017)

10081 Background: Cardiovascular disease (CVD) has been identified as a leading cause of mortality among cancer survivors, particularly long-term survivors. However, studies examining the prevalence of CVD risk factors and CVD-specific preventive care among US cancer survivors are lacking. We utilize the National Health Interview Survey (NHIS) data to address this knowledge gap. Methods: NHIS is an annual survey among roughly 88,000 individuals across the US, and its data are representative of US population-based estimates of health status, healthcare behavior, and healthcare utilization. 15,747 individuals surveyed from 2011 to 2015 who reported a history of cancer (except non-melanomatous skin cancer) were included in this study. Prevalence of CVD risk factors and preventive care received were calculated incorporating NHIS sample weights. A multivariable logistic regression model was used to evaluate factors associated with risk factor monitoring. Results: 55% of the cohort was ≥6 years out from cancer diagnosis and 53% were 65 years or older. CVD risk factors were prevalent across the entire cohort (Table). Among survivors &lt; 50 years, 30% were active smokers, and 35% obese. Among survivors ≥65, 40% had known CVD. Among survivors with each risk factor, rates of monitoring and management of each is reported in Table. On multivariable analysis, seeing a generalist was strongly associated with monitoring of blood pressure (OR 18), cholesterol (OR 8), and fasting glucose (OR 3). Conclusions: This study provides the current status of preventive care among US cancer survivors, illustrating that CVD and its risk factors are common. Rates of monitoring of hypertension and hyperlipidemia are high, but there is room for improvement in interventions targeting obesity and smoking cessation. [Table: see text]
TCT-548 Predictors of clinical outcomes after polymer free amphilimus- and biolimus-eluting stents: the FREE-FUTURE study
Authors: Giulio Stefanini, Mauro Chiarito, Cosmo Godino, Luca Testa, Altin Palloshi, Arturo Giordano, Franco Fabbiocchi, Anita Paggi, Francesco Bedogni, Corrado Tamburino, Carlo Briguori, Antonio Colombo, Gennaro Sardella
Journal: Journal of the American College of Cardiology (2018)
Effect of timing of vitamin B12 supplementation in patients receiving pemetrexed for treatment of advanced non-squamous non-small cell lung cancer or malignant pleural mesothelioma.
Authors: Zachary Schlei, Alison Meagher, Grace K. Dy, Karen Pfentner
Journal: Journal of Clinical Oncology (2016)

e21682 Background: Pemetrexed (Pem) is a folate analog inhibitor considered first line (1L) for advanced non-squamous non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Before the routine use of folic acid and vitamin (vit) B12 supplementation prior to initiating Pem, there were high rates of cytopenias. These rates have been reduced with vit B12 supplementation, but the optimal timing of supplementation has not been thoroughly investigated. Methods: This was a single center, retrospective chart review investigating patients (pts) treated in the 1L setting with > 2 cycles (C) of Pem, with or without a platinum agent, from January 1, 2012 to June 30, 2015, who received same-day vit B12 supplementation versus those who received it > 1 day prior to Pem administration. The objective was to evaluate safety outcomes in pts who received vit B12 same-day (group A) versus vit B12 administration > 1 day (group B) prior to Pem. Results: A total of 281 pts met inclusion criteria: 137 pts in group A and 144 pts in group B (median time of vit B12 administration prior to Pem; 7 days, range 1-42 days). There were no clinically significant differences between groups at baseline. Mean change in hemoglobin (HGB), platelet count, and absolute neutrophil count (ANC) from C1 to C2 or C2 to C3 did not differ significantly between groups. There were no significant differences in clinical events (neutropenic fever, hospitalization, or anemia) between C 1 and C2 or C2 and C3 requiring supportive care (antibiotics or transfusions). There was no difference in treatment delay > 7 days in C2 but a significant difference was noted in C3 [28/114 (24.6%) group A vs 14/118 (11.9%) group B, p = 0.0164]. In group A, significant predictors of delay in C3 were baseline HGB (mean 13.3 g/dL vs 12.4 g/dL, p = 0.0137) and ANC (mean 6 x109/L vs 5 x109/L, p = 0.0003). There was a significant difference in percent change in ANC from C1 to C2 (group A -28.4% vs group B -8.2%, p = 0.0419), but this did not result in C2 delay. Conclusions: Same-day administration of vit B12 and Pem is a safe practice in pts with NSCLC and MPM as there were no clinically meaningful changes in hematologic indices.