tbuckley/cabot-search huggingface dataset:
The value of patient-reported symptoms as prognostic factors for survival in advanced colorectal cancer
Authors: F. Efficace, A. Bottomley, C. Coens, K. van Steen, T. Conroy, P. Schoffski, H. J. Schmoll, E. van Cutsem, C. H. Köhne
Journal: Journal of Clinical Oncology (2005)

3585 Background: The study aims to evaluate if patient’s baseline self-reported symptoms independently predict survival in advanced colorectal cancer patients. This study uses data from a recently completed international randomized controlled trial (RCT) conducted by the European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Group. Methods: The overall sample consisted of 497 patients with previously untreated metastatic colorectal cancer who were randomly assigned to receive high-dose fluorouracil given as a weekly 24-hour infusion with or without leucovorin versus bolus fluorouracil plus leucovorin. Patients’ self reported symptoms at baseline were assessed using the EORTC QLQ-C30, and analyzed as continuous factors on seven pre-selected symptom related scales, scores ranging from 0 to 100. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. A stepwise (back and forward) variable selection procedure was used to identify independent factors prognostic for survival. Key biomedical variables were also included in the analysis. Results: The original RCT failed to show any differences between treatment arms in terms of overall survival (OS) and quality of life outcomes. The prognostic factor analysis was conducted on all available patients with baseline questionnaires (n=299). The final multivariate model identified the following clinical variables: white blood cell count (HR= 1.76; 95% CI=1.293 - 2.403; P<.001), alkaline phosphatase (HR=1.46; 95% CI=1.085–1.96; P=.01), performance status (HR=1.28; 95% CI=1.024–1.61; P=0.03) and number of sites involved (HR=1.09; 95% CI=1.009–1.181; P=.02). In addition to these clinical variables, fatigue also independently contributed to the prognostic information (HR=1.006; 95% CI=1.001–1.011; P=.01), resulting in a hazard increase of 6% for every 10-point shift on the fatigue symptom scale. Conclusion: Patients’ self reported fatigue levels appear to provide additional prognostic information beyond traditional medical data. Such information could help clinical management of individual cancer patients in routine clinical practice. No significant financial relationships to disclose.
Concomitant low-dose cisplatin and radiotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN): Analysis of survival and toxicity
Authors: H. Lau, D. Yee, J. Mackinnon, S. Brar, D. Hao, S. Gluck
Journal: Journal of Clinical Oncology (2004)

5555 Background: To assess the toxicity, response rate, overall and progression-free survival for locally advanced SCCHN using concurrent low-dose cisplatin and once-daily radiation (RT). Methods: From July 2000 to April 2003, 57 patients with locally advanced SCCHN were treated with a regimen of 3D conformal RT, 70 Gy over 7 weeks with concurrent cisplatin 20 mg/M2 during days 1 - 4 of weeks one and five. Eligible patients included stage II oropharyngeal (4), stage III (12), and stage IV (34) oropharyngeal, hypopharyngeal, and laryngeal SCC cancers. Patients with SCC of neck nodes with unknown primary were included if neck nodes were N2 or N3 category (7). Patients were evaluated by surgeon, radiation oncologist, and medical oncologist prior to treatment. Acute toxicities were graded weekly during treatment and in follow-up according to the RTOG / CTC toxicity criteria. Results: 57 patients were treated. Median age was 58 with 18 patients over the age of 65. All completed the prescribed radiation dose of 70 Gy. Chemotherapy compliance was as follows: 31 patients (54%) completed 100% of chemotherapy and the remainder completed >= 50% of chemotherapy. Complete response was noted in 45 (80%) of 56 evaluable patients. Treatment Toxicity: 27/57 (47%) of patients required hospitalization during treatment for supportive care. Grade 3 or 4 radiation mucositis, pharyngitis, or skin reactions was noted in 37 patients -grade 3 - (36); grade 4 - (1). Grade 3 or 4 hematologic toxicity was noted in 4 patients (7%). Median follow-up of all alive patients was 14.5 months. The actuarial 2 year overall and progression-free survival are 66% and 55%. Conclusions: This regimen appears tolerable and adds minimal excess toxicity compared to treatment with radiation alone. Our results are comparable to concurrent chemotherapy regimens using either high-dose cisplatin or multiagent chemotherapy. This regimen may be offered as an alternative to patients seeking organ preservation for locally advanced SCCHN, even in elderly patients or those with compromised performance status. No significant financial relationships to disclose.
Pathology of Tumors of the External Ear in Mice Induced by Ultraviolet Radiation
Authors: Hugh G. Grady, Harold F. Blum, John S. Kirby-Smith
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article Pathology of Tumors of the External Ear in Mice Induced by Ultraviolet Radiation Get access Hugh G. Grady, Hugh G. Grady acting assistant surgeon National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold F. Blum, Harold F. Blum senior pharmacologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar John S. Kirby-Smith John S. Kirby-Smith assistant physicist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 3, December 1941, Pages 269–276, https://doi.org/10.1093/jnci/2.3.269 Published: 01 December 1941
Whole blood collected after four days of filgrastim and reinfused after high dose myeloablative chemotherapy for various cancers is a safe and cost effective method of stem cell rescue
Authors: V. Raina, N. Lokeshwar, A. Sharma, G. M. Bhatt, R. Kumar
Journal: Journal of Clinical Oncology (2005)

6670 Background This study was undertaken to demonstrate the reconstitutive potential of reinfusion of whole blood after mobilization with filgrastim without cell separation and cryopreservation in the setting of high dose chemotherapy. Materials and Methods Twenty-nine patients suffering from Multiple Myeloma, Hodgkin’s and non-Hodgkin’s lymphoma and Germ Cell Tumors were included. Mobilization was done with filgrastim at a dose of 5 μg/Kg s.c. twice a day for 4 days. On day 5, 15 ml/Kg of whole blood was collected by venesection in standard blood donor bags with ACD in the ratio of 1:5 and stored at 40C for 24–120 hours. Immediately after collection, standard myeloablative chemotherapy was administered depending upon the underlying disease. Whole blood thus stored was infused back to the patient 24–48 hours after the last dose of chemotherapy over 2–3 hours. Filgratim at a dose of 5 μg/kg was given daily till neutrophil engraftment. Results The median age was 38 years (range 13–64 years). The median volume of blood collected was 1000 ml (range 800-1400 ml). The MNC was 2.1 X 108/Kg (range 0.7–4.0 X 108/Kg). All patients engrafted successfully except 1 who died of transplant related mortality on day 10. The median time to achieve ANC of > 0.5 X 109/L was 12 days (range 8–16 days) and platelet recovery to > 20 X 109/L was 14 days (range 7–55 days). Conclusions The procedure was 30% less expensive than a conventional autotransplant in this hospital. We conclude that infusion of whole blood after filgrastim, without cell separation and cryopreservation is a simple, efficacious and a less expensive alternative to PBSC transplant. These observations are particularly important in countries with limited resources No significant financial relationships to disclose.
Fusion changes patient management with PET &amp; C
Authors: S. R. Bunker, C. B. Dunleavy
Journal: Journal of Clinical Oncology (2004)

702 Background: Growing emphasis is placed on “fusion” of slices from Computed Tomography (CT) and Positron Emission Tomography (PET). 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET imaging has proven to be more accurate than conventional imaging in the staging and restaging of breast cancer. With “fused” images unique metabolic information from PET, with the simultaneously anatomic information from CT is useful for anatomic localization. Methods: Eligibility included referrals from physicians of patients for staging or restaging of breast cancer with FDG PET. The treatment was based on the use of a Philip's Allegro PET scanner. The primary endpoints were to determine the per cent change in patient management as well as sensitivity, specificity and accuracy. Follow up phone calls to referring physicians were made inquiring how PET findings altered clinical management decisions. Breast cancer patient's CT findings were compared to PET for accuracy, specificity and sensitivity. Results: The accrual of data demonstrated that 19 patients' CTs were co-registered for “fusion” with corresponding slices from whole body PET studies. The subsequent 3-D co-registration of the respective data sets provided unique information. Specifically, six patients were upstaged and four were down staged based on the recognition of false positive/negative PET findings and/or false positive/negative CT. Follow-up with referring physicians occurred over the twelve month period and the change in patient management averaged 30% with a confidence level of plus or minus 3%. Analysis included phone surveys of referring physicians inquiring about altered clinical management decisions of their patients and patient chart review. In our study, a 3-D software approach was utilized to “fuse” image data acquired at separate locations optimizing the two studies as they occur in the natural progression of referral algorithms. Conclusions: 34 cases with diagnosed breast cancer were referred for FDG PET imaging over a 12 month period. With PET studies a change in patient management occurred 30% of the time. Overall, PET studies were 90% more sensitive, 85% more specific, and 87% more accurate compared to CT. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fusion Diagnostic Group
Mutational analysis of signaling pathways in colorectal cancer
Authors: Victor E. Velculescu
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

SY15-2 

Although it is widely accepted that cancer is a genetic disease, many of the key oncogenes and suppressor genes involved in tumorigenesis remain to be identified. We have been interested in using genome-wide approaches to identify molecular differences between human cancer cells and normal cells. Using information from the Human Genome Project and high throughput sequencing approaches, we have begun to systematically analyze cancer genomes, starting with genes families involved in signal transduction. These efforts have recently identified frequent activating mutations in kinases and phosphatases not previously linked to human cancer. For example, we have found genetic alterations in the PIK3CA gene encoding the p110 alpha phosphatidylinositol 3-kinase in ∼30% of colon, breast and brain cancers, providing a rational target for therapy in a large fraction of common malignancies. The results of these studies and their implications for cancer diagnosis and therapy will be discussed.
Herbert Jonathan Kwaku-Mensah Mamattah
Authors: Joseph O E Jones
Journal: BMJ (2015)

Herbert Jonathan Kwaku-Mensah Mamattah’s parents were the chief of the Klevi clan and the queen mother of Keta in Ghana’s Volta region. Herbert grew up in the royal family, destined to become a priest, but quit the seminary at a very advanced stage to pursue a career in medicine instead. In 1962 he qualified at University College Hospital, Ibadan, in Nigeria, where he did his house officer jobs before becoming a registrar in pathology under Professor David Goldsmith Montefiore, a pathologist and pioneering microbiologist and …
Simultaneous Activation of Signals Through gp130, c-kit, and Interleukin-3 Receptor Promotes a Trilineage Blood Cell Production in the Absence of Terminally Acting Lineage-Specific Factors
Authors: Takafumi Kimura, Hideaki Sakabe, Shigeatsu Tanimukai, Tatsuo Abe, Yoji Urata, Kiyoshi Yasukawa, Akira Okano, Tetsuya Taga, Haruo Sugiyama, Tadamitsu Kishimoto, Yoshiaki Sonoda
Journal: Blood (1997)
Decitabine effect on human tumor expression of various transporters
Authors: D. J. Stewart, M. I. Nunez, J. Jelinek, Z. Guo, D. Hong, S. Gupta, Y. Oki, J. Issa, R. Kurzrock, I. I. Wistuba
Journal: Journal of Clinical Oncology (2009)

2540 Background: We reported that immunohistochemistry (IHC) expression of the platinum/copper transporter CTR1 in human tumors correlated inversely with DNA methylation and was increased by the DNA demethylating agent decitabine (D. Stewart et al, Proc ASCO 2008). Decitabine also increased expression of folate transporters in platinum-resistant cell lines that have decreased expression of folate transporters and of small GTPases such as RHOA that regulate endocytosis (D Shen et al. Br J Cancer 2004). Methods: Tumors were biopsied pre decitabine and on cycle 1 day 12 in 31 patients with refractory malignancies in a phase I study of decitabine given days 1–5 ± 8–12 each cycle. We used IHC to assess the folate carriers FOLR1 and RFC1, the glucose transporter GLUT4 and the endocytosis regulating small GTPase RHOA. Scores of 0–300 were calculated by multiplying staining intensity (0–3) by % cells staining. LINE assays were used to assess % global DNA methylation. Results: DNA methylation did not correlate with FOLR1, RFC1 and GLUT4 scores but did correlate inversely with RHOA (r= -0.58, p=0.006). Median tumor IHC scores post vs pre decitabine were 80 vs 80 (range, 0–270 vs 0–210, p=0.89) for FOLR1, 90 vs 90 (range, 15–300 vs 0–300, p=0.17) for RFC1, 0 vs 0 (range 0- 140 vs 0–70, p=0.61) for GLUT4, and 77.5 vs 50 (range, 0–210 vs 0–210, p=0.03) for RHOA. If only tumors with pre decitabine scores &lt;150 were included, post vs pre RFC1 differences were significant (95 vs 80, p=0.004). Outcomes were similar whether or not 4 melanoma patients (in whom melanin pigment decreased the reliability of IHC scoring) were included. Conclusions: As previously noted with the copper/platinum transporter CTR1, treatment with the DNA demethylating agent decitabine was associated with a significant increase in tumor expression of the endocytosis regulator RHOA in resistant human tumors. Expression of the folate transporter RFC1 was also increased if only patients with levels that were initially low were included. This suggests that decitabine should be tested for its ability to increase uptake of chemotherapy in resistant tumors. Promoter methylation for these transporters has not yet been assessed. Supported in part by NIH grant UO1 CA062461–10 &amp; R21 CA112895–01A1. No significant financial relationships to disclose.
Geographical differences in acute treatment-related toxicity frequencies: A comparative analysis of 503 colorectal cancer (CRC) patients receiving chemotherapy
Authors: G. Aprile, E. Iaiza, F. De Pauli, E. Zanon, L. Foltran, M. Mazzer, G. Cardellino, M. Miscoria, G. Fasola, S. Sonis
Journal: Journal of Clinical Oncology (2008)

20561 Background: Race, gender, gene expression, and age have all been reported to affect the risk of regimen-related toxicities. Although the risk could vary across geographic differences, this factor has not been studied. Aim of this study was to compare the frequencies of regimen-related acute toxicities between American and Italian CRC patients. Methods: Electronic medical charts of 503 patients treated with oxaliplatin, irinotecan, and/or 5-Fluorouracil based regimens were reviewed. The populations were matched for median age, sex, race, and stage of disease. Baseline demographics, clinical information, and overall incidence of treatment-related NCI-CTC toxicities reported during the first two cycles of chemotherapy were recorded. We selected for comparison only toxicities with a reported frequency of at least 10% in the original American cohort. Chi-square test was used for comparison. Results: The overall incidence of gastrointestinal and constitutional toxicities was more in the American cohort, while Italian patients experienced an higher rate of pain and sensory neuropathy, probably due to an higher oxaliplatin exposition (67 versus 49%). Most of the observed differences were confined to grade 1 toxicities Conclusions: In general, compared to American CRC patients, Italian patients experience less acute toxicity following cycle 1 and cycle 2 chemotherapy Toxicity (any grade) US pts, cy 1 (n=300), % Italian pts, cy 1 (n=203), % p value US pts, cy 2 (n=297), % Italian pts, cy 2 (n=203), % p value dyspepsia 10,0 7,5 p=0.361 22.6 11.3 p=0.004 dehydration 10,7 4,5 p=0.016 13.8 3.9 p=0.001 palpitation 11,7 5 p=0.014 11.8 4.4 p=0.007 fever 14,0 6,5 p=0.013 16.5 8.9 p=0.022 bloating 16,7 7 p<0.001 21.9 9.9 p=0.001 pain 17,7 21 p=0.402 17.2 26.6 p=0.024 vomiting 21,7 11 p<0.001 25.3 10.8 P<0.001 sensory neuropathy 22,3 32 p=0.038 28.3 44.8 p=0.002 mucositis 24,7 22,5 p=0.953 45.8 28.1 p=0.003 anorexia 25,0 7,5 p<0.001 32.3 12.3 p<0.001 diarrhea 50,0 24.5 p<0.001 66.0 22.7 p<0.001 asthenia/fatigue 55,3 46,5 p=0.179 73.7 54.7 p=0.01 nausea 56,7 37,5 p<0.001 68.0 37.0 p<0.001 No significant financial relationships to disclose.
Detection of breast cancer cells in the bone marrow of early breast cancer patients using quantitative RT PCR for CEA
Authors: F. Janku, G. Korinkova, J. Srovnal, Z. Kleibl, J. Novotny, L. Petruzelka, B. Matous, M. Hajduch
Journal: Journal of Clinical Oncology (2005)

9638 Background: Carcinoembryonic antigen (CEA) is widely used as a serum tumor marker. Several systems for the CEA-RT-PCR approach have been reported to date. In this study, we have evaluated quantitative CEA-RT-PCR as a diagnostic tool for detection of isolated tumor cells in the bone marrow of early breast cancer patients prior adjuvant systemic therapy. Methods: We obtained bone marrow aspirates from 70 patients with stage I (37%), II (60%), and III (3%) breast cancer who underwent either immediate complete resection of the tumor or were planned for neoadjuvant therapy with subsequent curative surgery. mRNA was isolated using QIAamp RNA blood mini kit (Qiagen). Subsequently quantitative RT-PCR for the expression of CEA was performed. Results: CEA was detected in samples from 29 (41%) out of 70 patients. With a median follow-up of 22 month we observed 6 recurrences, two in patients with positive bone marrow. At the time of analysis 2 patients died. None of these deaths were tumor related. CEA in the bone marrow did not significantly correlate with other prognostic variables, e.g. tumor size, lymph nodes involvement, tumor grade, hormonal receptor status, HER2/neu expression, and histologic type. Disease free and overall survival did not significantly differ with respect to CEA in the bone marrow. Conclusions: RT-PCR assay for CEA is a useful and sensitive tool for detection of occult breast cancer cells in the bone marrow. Clinical and prognostic relevance of minimal residual disease detected using RT- PCR remains unclear and should be further investigated. No significant financial relationships to disclose.
Assessment of airway neutrophil activation in adult non-eosinophilic asthma
Authors: Collin Brooks, Christine van Dalen, Elizabeth Harding, Ian Hermans, Jeroen Douwes
Journal: European Respiratory Journal (2011)

Background:  It is now evident that there are different pathophysiologies underlying different asthma phenotypes. The neutrophil has been proposed to be a principal cell type involved in non-eosinophilic asthma (NEA).   Aims:  To investigate different aspects of neutrophil activation in NEA.   Methods:  24 adult asthmatics (9 eosinophilic asthma (EA>2% sputum eosinophils), 15 NEA) and 18 healthy controls were recruited by advertisement and successfully underwent clinical assessment, spirometry and sputum induction. Sputum was analysed for neutrophil number (differential cell count), levels of neutrophil-associated soluble mediators (myeloperoxidase (MPO), IL-8 and MMP-9, by ELISA) and neutrophil expression of CD11b (flow cytometry).   Results:  Only one asthmatic individual in our study was neutrophilic (>61% neutrophils). EA was generally associated with a more severe clinical phenotype and poorer control (40% poorly controlled) than NEA (8%). There was no statistically significant difference in percentage of sputum neutrophils, neutrophil expression of CD11b, or sputum levels of MPO, IL-8 or MMP-9, between EA, NEA or control subjects. However, we observed that neutrophil percentage increased with age regardless of disease status (R S =0.71, p S =0.36, p=0.02), and MMP-9 (R S =0.55, p=0.0002).   Conclusions:  Our results show no difference in neutrophil activation in NEA compared to either EA or healthy controls. They also support previous data showing an increase in neutrophil number with aging in both asthma and healthy controls, and suggest that age must be appropriately controlled for when defining a neutrophilic asthma phenotype.
Herpes simplex virus infection in the immunocompromised cancer patient.
Authors: C I Bustamante, J C Wade
Journal: Journal of Clinical Oncology (1991)

The development of infection remains a significant source of morbidity and mortality in the oncology patient. This patient population is at increased risk for infection because of alterations in cell-mediated immunity generated by the underlying neoplastic process and/or immunosuppressive therapy. Viral infection, particularly that attributable to herpes simplex virus (HSV), is being seen with increased frequency in the oncology patient. Because effective therapy is available with the early use of antiviral agents, it is important to be aware of the potential for viral infection and to recognize the signs and symptoms that are evident early in its course. An overview of HSV infection is provided here, including discussion of the virus itself, its pathogenesis, its clinical spectrum, and current prophylactic and therapeutic approaches.