tbuckley/cabot-search huggingface dataset:
Clinical and immunological responses to a DNA fusion vaccine in patients with carcinoembryonic antigen-expressing tumors: A Cancer Research UK phase I/II study.
Authors: C. H. Ottensmeier, A. Mander, K. McCann, L. Low, E. Hall, A. Bateman, S. Clive, D. A. Anthoney, F. K. Stevenson, A. O'Callaghan
Journal: Journal of Clinical Oncology (2010)

2579 Background: We have designed DNA fusion vaccines encoding a tumor-derived peptide, linked to a tolerance-breaking domain sequence (DOM) from tetanus toxin. One peptide sequence from prostate cancer is in clinical trial with CD8+ T-cell responses detected in 60% of patients. For patients with CEA expressing cancers, the target peptide is an HLA-A2-binding sequence, CAP-1 (CEA605–613). Methods: We undertook a single dose level, two-arm phase I/II study to examine the safety and immunogenicity of the DNA fusion vaccine (p.DOM-CAP-1) in patients with CEA-expressing cancers (bowel, lung, and breast cancer). 1mg/dose of DNA was given at weeks 0, 1, 2, 4, 8 and 12. 15 patients with measurable disease were recruited to arm I, 12 patients without radiological evidence of disease to arm II of the study. Results: Interim immunological results reveal humoral and cellular responses to the DOM vaccine component in both arms, confirming successful delivery of the vaccine. CAP1–specific CD8+ T-cells were detected using ex vivo and cultured IFNγ ELISPOT, demonstrating CAP-1 antigenicity. To date immune assessment is mainly in patients with advanced disease (15/15 arm I, 5/12 arm II). In these 20 patients 50% have developed a FrC cellular responses, 35% a CAP-1 cellular response. Follow-up is almost complete with 1 timepoint each in two patients outstanding. We observed an unexpected, high incidence of gastrointestinal adverse events (GI AE) notably diarrhoea (12/27) in vaccinated patients, not observed in the trial of prostate cancer patients. This occurred early after vaccination in patients both with and without measurable disease. In arm 1 these adverse events appear to be coincident with an increased time to clinical and radiological disease progression, longer on-study follow up, decreases in, or stable CEA levels, and longer duration of positive anti-DOM cellular responses (mean 35±14 weeks compared to 7.5± 5 weeks [p<0.006] for those without diarrhea). Conclusions: The early clinical and immunological data indicate that the vaccine is immunogenic. Immune responses correlate with GI-associated effects and an increased time to disease progression. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genvax Genvax Genvax
Firstline chemotherapy with nedaplatin (CDGP) and irinotecan (CPT-11) for the patients with adenocarcinoma of uterine cervix: A pilot study
Authors: M. Yoshida, M. Tanaka, M. Kimura, T. Taguchi, D. Ogishima, M. Nojima, Y. Furugen, K. Kinoshita
Journal: Journal of Clinical Oncology (2005)

5155 Background: We conducted a pilot study to evaluate the feasibility, response rate, and toxicity of nedaplatin (CDGP) and irinotecan (CPT-11) as a firstline chemotherapy for the patients with adenocarcinoma of uterine cervix. Methods: Following or prior to cytoreductive surgery, eligible patients; no prior systemic chemotherapy; WHO PS 0–1 and adequate bone marrow, renal and hepatic function were treated with CDGP (80 mg/m2 on d1 q 4 weeks), CPT-11 (80 mg/m2 on d1, 8 and 15). Colony-stimulating factors were used at the discretion of the treating physician. Chinese medicine was initiated one week before the CDGP to avoid severe diarrhea Results: 9 patients (median age = 51.1; range 30–72) were enrolled; 3 patients were stage II, 1 patient was stage III, 5 patients were stage IV. Histologically, 1 were adenosquamous, 8 were adeno type carcinoma. A total of 40 cycles of chemotherapy were administerd. Grade 3 and 4 neutropenia developed in 26.5% and 20.6% respectively. Grade 3 and 4 thrombocytopenia developed in 20.6% and 0% respectively. One (11.1%) patient exhibited a complete response and 6 (66.7%) patients demonstrated a partial response, for total response rate of 77.8%, although there was no reported interference with activities of daily living. The patients’ median duration of observation and median overall survival was 36 months (ranged 33 to 39 months) and 12 months (ranged 4 to 12 months), respectively. Two of the original 9 patients were alive at the conclusion of data collection. Conclusions: Nedaplatin (CDGP) and ilinotecan (CDGP) shows positive activity, with acceptable toxicity and is able to prolong progression free interval as a first line chemotherapy for the patients with adenocarcinoma of uterine cervix. No significant financial relationships to disclose.
National study of patients, caregivers and physicians reveals pain associated with advanced prostate cancer as the primary concern
Authors: M. A. Moyad, T. A. Kirk
Journal: Journal of Clinical Oncology (2006)

14505 Background: Over 50,000 men developed hormone refractory prostate cancer (HRPC) in 2005 (CancerMetrics 2005). The objective of this study is to compare attitudes of patients, caregivers and physicians on the effects of advancing disease on patients. Methods: Respondents indicated attitudes towards 18 PC symptoms. Responses were analyzed by a division of Yankelovich. Grant funding from Abbott.Us TOO International conducted an online survey of HRPC patients, caregivers, and physicians in 2005. Patients and caregivers were recruited from NexCura’s database of users of the Treatment Profiler Options Tool for PC and links from PC websites (UsTOO, PCRI, PCF and PAACT). Board certified physicians who treat HRPC were recruited by J. Reckner &amp; Associates. Respondents indicated their attitudes towards 18 symptoms of advancing PC. Responses were analyzed by TSC, a division of Yankelovich. Results: 409 HRPC patients (P), 236 caregivers (C), and 204 physicians (MD) (100 urologists/104 oncologists) participated in the study. Mean patient age was 65.7 and age at diagnosis was 60.2. Patients were identified as non-metastatic (M0) or metastatic (M+). 46% of patients were M+; 60% of caregivers are caring for M+ patients. 51% of M+ patients and 74% of M+ caregivers’ patients experienced bone pain. The most common symptom concerns were bone pain, other pain and mental changes. Conclusions: Over half of the M+ patients experienced bone pain related to PC in this survey. Once HRPC becomes M+, bone pain significantly affects the quality of life of patients and caregivers. It is the highest rated concern of patients, caregivers and physicians. Bone pain significantly alters the lives of those with advancing HRPC. New options are needed for patients with advancing PC. [Table: see text] [Table: see text]
A multi-transcript blood signature for detection and assessment of gut neuroendocrine tumors.
Authors: Mark S. Kidd, Daniele Alaimo, Stephen Callahan, Nancy Smith Texeira, Ignat Drozdov, Irvin Mark Modlin
Journal: Journal of Clinical Oncology (2014)

216 Background: Gut neuroendocrine tumors (NETs or “carcinoids”) are difficult to manage since they present with advanced disease and limited treatment options are available. Imaging is relatively insensitive in identifying treatment efficacy and the current biomarker, a neurosecretory peptide, Chromogranin A (CgA), has limited value. There is a lack of specific blood biomarker tests both to detect tumors and measure treatment responsiveness. We report the utility of a 51 marker peripheral blood signature (NETest) in comparison to CgA. Methods: The signature was validated using a 2-step qPCR method for detecting NETs in two sets (n=115; n=120) and for measuring treatment responses in a third set (n=133, including complete remission: n=4, clinically stable disease: n=82 and non-responders/clinically progressive disease: n=47). Comparison with CgA (DAKO-ELISA) was undertaken. The confounding effects of PPIs, age, sex and race were also determined for the PCR test. Results: The PCR NETest detected NETs with high sensitivity (85-98%) and specificity (93-97%). It identified pancreatic and gastrointestinal NETs with similar efficacy (&gt;85%) as well as metastatic and non-metastatic lesions. NETest score was significantly reduced (p&lt;0.004) following surgery or RFA and significantly higher in clinically progressive disease compared to stable disease (5.8±0.3 versus 0.6±0.1, p&lt;0.002). The performance metrics for differentiating stable and progressive disease were sensitivity: 91% and specificity: 91%. The score was robust (reproducibility: Coefficient of Variation&lt;2%).Long-term PPI use (&gt;1yr), did not alter the NETest values, neither did age, sex or ethnicity. The PCR score was significantly (p&lt;0.0005) more accurate than CgA for identifying NETs and was elevated in 91% of NETs when CgA was normal. Conclusions: This study demonstrates that a multi (51)-gene NET panel is both sensitive and specific for detecting NETs and is capable of differentiating clinically stable from progressive disease. The test is robust and significantly more sensitive and specific (accurate) than CgA. The NETest thus facilitates both accurate disease detection, and disease progress thereby permitting assessment of treatment efficacy.
Identification of a new genetico-histological subset of posterior fossa ependymoma: "Biphasic ependymoma"
Authors: Thomas Palm, Catherine Godfraind, Isabelle Salmon, Dominique Figarella-Branger, FrancOise Chapon, Catherine Lacroix, FrancOise Gray, David Ellison, Miikka Vikkula
Journal: Neuro-Oncology (2008)
The follow-up sought after diagnosis of a <i>BRCA-1</i> or <i>BRCA-2</i> mutation.
Authors: Karinn Marie Chambers, Edward Joey Armstrong, Teresa Flippo, Terry Sarantou, Frederick L. Greene, Wendy Brick, Brook White, Lisa Amacker-North, Richard L. White
Journal: Journal of Clinical Oncology (2012)

57 Background: A woman with a known BRCA mutation has a lifetime risk for the development of breast cancer of up to 80%. Carolinas Medical Center cares for approximately 600 breast cancer patients annually with genetic testing offered to those patients whose history meets commonly established criteria. This study seeks to document the follow-up patients with BRCA mutations most commonly undertake at our facility. Methods: This study is a retrospective review of all patients who underwent genetic testing at Carolinas Medical Center and who were found to be positive for a mutation in the BRCA gene. Since 1996 our genetics group has tested 2056 individuals, of these 246 (12%) carry a mutation of the BRCA-1 and/or BRCA-2 gene. 102 of these 246 patients (41%) had no evidence of cancer at the time of genetic testing. 144 of these 246 patients (59%) did carry a diagnosis of cancer at the time of genetic testing. Results: Of the 246 patients who tested positive for a deleterious mutation in the BRCA gene 204 (83%) had documented follow-up after their diagnosis. 140 of those 204 patients (69%) had documented initial follow-up appointments to discuss their diagnosis. 63 patients of the 140 (45%) who sought initial consultation met with a surgeon. 73 of these 140 patients (52%) had their initial consultation with a Gyn/Oncologist. 3 patients had their initial consultation with a medical oncologist and the remaining patient with their primary care physician. Documentation was available for 131 of the 204 patients (64%) in regards to follow up related to their risk of breast cancer development, 129 of those patients were being followed by a high risk breast provider. 126 of the 204 patients (62%) with long term follow-up were being followed by a Gyn/Oncologist secondary to their increased risk for ovarian cancer. This data includes all patients regardless of the decisions they made concerning surveillance or prophylactic surgery. Conclusions: The majority of the patients at Carolinas Medical Center who have tested positive for a BRCA mutation have sought long term follow-up with both a high risk breast provider and a Gyn/Oncologist in regards to their increased risk for the development of both breast and ovarian cancer.
African Americans with hepatocellular carcinoma have worse survival than Caucasians: A tumor registry study
Authors: J. Chugh-Sachdev, M. Sachdev, R. Womeodu, K. Wright, D. Przepiorka
Journal: Journal of Clinical Oncology (2005)

6062 Background: SEER data suggest an increasing incidence of hepatocellular carcinoma (HCC) in the US, and overall 5-year survival is less than 5%. Which subgroups of patients with HCC have the poorest prognosis is not known. Methods: To determine what factors affect survival of HCC patients and if survival has changed significantly in the last three decades, we performed a retrospective analysis of 193 consecutive patients diagnosed from 1971–2000 with HCC, identified from a hospital tumor registry. Cox regression analysis was performed to identify demographic variables prognostic for survival. Results: The study cohort comprised 193 patients, (106 Caucasians, 84 African American (AA), and 3 other). There were 73 females and 120 males. The median age at diagnosis for the cohort was 67 years (range 13–90 years). Median survival for the entire cohort was 77 days. Patients were divided into 3 groups based on decade of diagnosis. Group 1 included 47 patients diagnosed from 1971–80, group 2 had 63 patients diagnosed 1981–90, and group 3 had 83 patients diagnosed 1991–2000. Overall survival did not change over the three decades (p = 0.94) for the entire cohort and for both races. In a multivariate analysis, AA race was significantly predictive of poorer survival (HR 1.45, 95% CI 1.07–1.96, p = 0.017), but age, gender and decade of diagnosis were not independent risk factors. AA patients had a significantly lower overall survival when compared to their Caucasian counterparts only in the last decade of analysis (p = 0.026) with a trend towards significance in the second decade (p = 0.083). Conclusions: We conclude that survival for HCC patients has remained low over the last three decades, and AA race is a significant predictor of poor survival. More studies are needed to determine what biological factors lead to the poorer survival for AA patients. No significant financial relationships to disclose.
Phase I and II study of OSI-774 and docetaxel in squamous cell carcinoma of the head and neck (SCCHN)
Authors: C. A. Rhoades, E. Kraut, D. Schuller, Y. Zhang, K. Chan, K. Lang, C. Eng, M. Grever
Journal: Journal of Clinical Oncology (2004)

5541 Background: OSI-774 is an inhibitor of the epidermal growth factor receptor tyrosine kinase that has activity in SCCHN. Docetaxel is active in SCCHN and has moderate toxicity when administered on a weekly schedule. We sought to determine the maximum tolerated dose (MTD) of OSI-774/weekly docetaxel in SCCHN. Methods: Patient (pt) eligibility: measurable recurrent or metastatic SCCHN considered incurable by surgery or radiation; ≤ 1 prior chemotherapy; ECOG performance status (PS) ≤ 2. Treatment regimen: oral OSI-774 daily for 28 day cycle; docetaxel on days 8, 15 and 22; cycle repeated every 28 days to a maximum of 6 cycles. Cohorts of 3–6 pts in each dose level. Plasma levels of OSI-774 and active metabolite OSI-420 were measured on Day 1 and 8. Results: To date, 15 patient have been enrolled with the following characteristics: (medians) age 57 years (range 24–78); PS 1 (range 0–2); 5 pts with prior chemotherapy. Initial dose level was 50mg:35mg/m2 (OSI-774:docetaxel) with no dose limiting toxicity (DLT) in cohort. Second cohort treated with 100mg:35mg/m2, two patients had DLT (one with rash and one with neutropenia/sepsis). Subsequent dose was lowered to 100mg:25mg/m2 and two of six pts developed DLT (one with rash and one with stomatitis). Fourth cohort was treated at 50mg:25mg/m2 dose. One of three pts developed unexplained pulmonary complications and 3 pts will be added to this cohort. In total, nine pts have experienced rash, two at grade 3 level. Twelve pts are response-evaluable; 4 partial responses, 6 with stable disease, 2 with disease progression. Three pts were not evalauble due to adverse event. Pharmacokinctic data does not explain need for lower dose in this combination. Conclusions: OSI-774/docetaxel is active regimen in SCCHN. The MTD is yet to be determined, but dose of combination therapy appears to be lower then single agent therapy with either drug. Biological correlative studies have been initiated. Patient accural continues with plan to proceed to phase II once MTD is determined. Updated data including pharmacokinetics and biological correlates will be presented. Disclosure: Trial supported by National Cancer Institute, grant #2 U01 CA 76576–06. No significant financial relationships to disclose.
A multicenter stratified phase II study of cetuximab for the treatment of patients with recurrent high-grade glioma
Authors: B. Neyns, J. Sadones, E. Joosens, F. Bouttens, L. Verbeke, J. F. Baurain, L. D'Hondt, C. Chaskis, A. Michotte, J. De Greve
Journal: Journal of Clinical Oncology (2008)

2017 Background: An increased copy number and mutation of the epidermal growth factor receptor (EGFR) gene are frequently found in high-grade gliomas (HGG). We investigated the activity of the EGFR-blocking monoclonal antibody cetuximab for the treatment of patients (pts) with recurrent HGG following surgery, radiotherapy, and chemotherapy. Methods: Eligible adult pts were treated with cetuximab (400 mg/m2 2 h IV on d1 and weekly 250 mg/m2 1h IV thereafter). Pts were stratified in 2 treatment arms according to the amplification status of the EGFR gene of their HGG (determined by fluorescence in situ hybridization on archival tumor material). Results: Between May 2005 and December 2007 a total of 55 pts with performance status 0–2 initiated treatment with cetuximab (28 pts with and 27 pts without an increased EGFR copy number, 17F/38M, median age 53 years [range 32–73]). Cetuximab was generally well tolerated. During a total of 689 treatment weeks the most frequent treatment-related adverse events were: skin toxicity (grade 2, n=12; grade 3, n=4), thrombocytopenia (grade 2, n=1; grade 3, n=2), confusion/diminished consciousness (grade 3, n=4 pt), lymphopenia (grade 4, n=1), infusion related allergic reaction (grade 2, n=1), intratumoral hemorrhage (grade 2, n=1), diarrhea (grade 2, n=1), and fatigue (grade 2, n=3). A dose reduction of cetuximab (to 200 mg/m² weekly) was necessary in 2 pts. After a median follow-up of 15 months, 11 pts are alive (5 are still receiving cetuximab) and 44 pts have died. The disease control rate was 35% (3 pts (5.6%) had a PR and 16 pts (29.6%) had SD) and 35 pts (64.8%) had PD. The median PFS was 1.9 months, median OS was 5.0 months. The 6-month PFS and OS rates were 10% and 40%, respectively. Whereas PFS was less than 5 months in the majority (n=49) of pts, a subgroup of 5 pts (9.2%) have a PFS on cetuximab of more than 9 months (range 9.5 to >16.5). No significant correlation was found between response, survival and EGFR copy number. Conclusions: Cetuximab as a single agent was safe and well tolerated in this population of pretreated patients with recurrent high-grade glioma. Durable disease control was observed in a small subgroup of patients. Mature results of this study will be available for presentation at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Merck, sanofi-aventis, Schering-Plough, Wyeth Merck
Ongoing outbreak of invasive listeriosis, Germany, 2012 to 2015
Authors: Werner Ruppitsch, Rita Prager, Sven Halbedel, Patrick Hyden, Ariane Pietzka, Steliana Huhulescu, Dorothee Lohr, Katharina Schönberger, Elisabeth Aichinger, Anja Hauri, Klaus Stark, Sabine Vygen, Erhard Tietze, Franz Allerberger, Hendrik Wilking
Journal: Eurosurveillance (2015)

Listeriosis patient isolates in Germany have shown a new identical pulsed-field gel electrophoresis (PFGE) pattern since 2012 (n = 66). Almost all isolates ( Listeria monocytogenes serotype 1/2a) belonged to cases living in southern Germany, indicating an outbreak with a so far unknown source. Case numbers in 2015 are high (n = 28). No outbreak cases outside Germany have been reported. Next generation sequencing revealed the unique cluster type CT1248 and confirmed the outbreak. Investigations into the source are ongoing.
24-hour arterial stiffness monitoring values in patients with COPD
Authors: Nina Karoli, Gulnara Dolishnyaya, Andrey Rebrov
Journal: European Respiratory Journal (2013)

Purpose.  The aim of the study was analysis of twenty-four-hour arterial rigidity (AR) monitoring values in patients with chronic obstructive pulmonary disease (COPD) in different stage of disease with arterial hypertension (AH).   Methods.  The study included 58 male patients with COPD and AH. Mean age was 63.3±8.9 years. Duration of disease was 7.5±5.7 years for COPD and 5.8±5.7 years for AH. All patients were divided into three groups. There were 18 patients with moderate COPD, 21 patients with severe COPD and 19 patients with very severe obstruction. Comparison group included 50 male patients with essential AH without chronic respiratory diseases, control group - 22 healthy male individuals. Twenty-four-hour AR monitoring measurement was performed using BPLab® MnSDP-2 apparatus (Petr Telegin, Russia). For assessment of AR we used pulse transit time (PTT2), (dP/dt)max and augmentation index (AIx) indexes. Values of AIx less than -10% a normal, and values greater than or equal to -10% are pathological.   Results.  In patients with severe and very severe COPD significant decrease of PTT2 index, increase of AIx versus patients of comparison group and control subjects have been observed (p   Conclusion.  Pronounced increasing of AR is most common in patients with severe and very severe COPD. We observed circadian variation of AR parameters with prevalence of nocturnal abnormality.
Pulmonary function after whole lung radiation in pediatric patients with malignant solid tumors
Authors: H. Inaba, L. Zhu, K. Srivastava, M. M. Hudson, M. S. Motosue, D. C. Stokes, V. McPherson, S. Srinivasan, M. J. Krasin, D. M. Green, S. L. Spunt
Journal: Journal of Clinical Oncology (2009)

10025 Background: Pediatric malignant solid tumors are increasingly curable; whole lung irradiation (WLI) may be used to treat pulmonary tumor involvement. Few studies have addressed long-term pulmonary function after WLI during childhood. Methods: We conducted a retrospective review of pulmonary function tests (PFTs) in 1 year survivors of pediatric malignant solid tumors treated with WLI. We assessed PFT changes over time and the relationship of abnormal values to clinical parameters (diagnosis, radiation dose, and presence or absence of boost lung irradiation or surgical resection). Results: We evaluated 164 PFTs performed on 49 patients with the diagnoses of Wilms tumor (38), rhabdomyosarcoma (5), Ewing sarcoma (3), synovial sarcoma (2), and thymoma (1). Median age at radiation was 6.3 years (range, 0.5–20.2 years); median WLI dose was 12 Gy (range, 10.5–18 Gy). Seventeen (34.7%) had focal pulmonary boost irradiation and 21 (42.9%) had partial lung resection. Across the entire population, forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) declined after irradiation with a median follow-up of 9.3 years. The odds of having a normal FEV 1 and FVC decreased by a factor of 0.90 (p = 0.0387) and 0.91 (p = 0.0445), respectively, every year, indicating that the proportion of patients with normal values of FEV 1 and FVC decreases over time. FEV 1 /FVC ratio and forced expiratory flow (FEF 25%-75% ) remained stable. Abnormal FEV 1 /FVC and FEF 25%-75% were more likely in patients who received boost irradiation than in patients who did not (p = 0.0034 and 0.0233, respectively). Conclusions: Pulmonary function worsened over time in this cohort of childhood cancer survivors treated with WLI. Boost irradiation further impaired pulmonary function. Further studies are planned to assess the clinical consequences of these progressive PFT abnormalities and to identify risk factors associated with clinically significant pulmonary dysfunction after WLI. No significant financial relationships to disclose.