tbuckley/cabot-search huggingface dataset:
The incidence of non-melanoma skin cancer after a single field treatment with aminolevulinic acid and blue light photodynamic therapy
Authors: O. N. Kozyreva, N. Konnikov
Journal: Journal of Clinical Oncology (2009)

e14646 Background: Non-melanoma skin cancer (NMSC) is the most common form of human cancer. Aminolevulinic acid photodynamic therapy (ALA PDT) is a safe and effective treatment for NMSC precursors. It is unknown if ALA PDT treatment will affect incidence of NMSC in high risk patients (pts). Methods: A retrospective study was undertaken using a Veteran Affairs Boston Health Care System Medical Record Database. Study population included immunocompetent pts with history of NMSC, multiple actinic keratosis (AKs), and moderate to severe dermatoheliosis (DH). Study pts received a single application of 20 % ALA to the face or scalp following by exposure to blue light at 10 J/cm2. Differences in incidence of NMSC two years prior and two years after ALA PDT were tested using the Wilcoxon rank sum test. Data were analyzed by the median and interquartile range (IQR). Results: 43 Caucasian males (range 59- 87 yrs), 37 (87%) had history of NMSC on the face or scalp, 32 (78%) had basal cell carcinoma (BCC), 11 (22%) squamous cell carcinoma (SCC), 100% of patients had multiple (&gt;4) AKs prior to treatment and 23 (75% ) had moderate to severe DH determined by Griffiths scale. Prior to ALA-PDT 74 NMSC's were documented: 40 (54%) BCC and 34 (46%) SCC. 46 NMSC's were documented following ALA-PDT: 22 (48%) BCC and 24 (52%) SCC. Prior to ALA-PDT, the frequency of BCC averaged 2 [IQR 1 to 3, max=4], and the frequency of SCC averaged 1 [IQR 1 to 1, max=3]. Following ALA-PDT, the occurrence of BCC averaged 1 [IQR 0 to 1, max=5], and that of SCC averaged 1 [IQR 0 to 2, max= 4]. The difference between BCC frequency before and after ALA-PDT treatment shown a significant reduction in BCC incidence (P = 0.0018). No such differences were observed between the frequency of SCC before and after ALA-PDT (P=0.6230) Conclusions: A single ALA-PDT treatment to the face or scalp in high risk patients significantly reduces the incidence of BCC, the incidence of SCC was not reduced. The potential role of ALA PDT as a NMSC chemopreventive modality warrants further investigation in larger samples with an alternative treatment protocols. No significant financial relationships to disclose.
IL6 Trans-signaling Promotes KRAS-Driven Lung Carcinogenesis
Authors: Gavin D. Brooks, Louise McLeod, Sultan Alhayyani, Alistair Miller, Prudence A. Russell, Walter Ferlin, Stefan Rose-John, Saleela Ruwanpura, Brendan J. Jenkins
Journal: Cancer Research (2016)

Oncogenic KRAS mutations occur frequently in lung adenocarcinoma. The signaling pathways activated by IL6 promote Kras-driven lung tumorigenesis, but the basis for this cooperation is uncertain. In this study, we used the gp130(F/F) (Il6st) knock-in mouse model to examine the pathogenic contribution of hyperactivation of the STAT3 arm of IL6 signaling on KRAS-driven lung tumorigenesis. Malignant growths in the gp130(F/F):Kras(G12D) model displayed features of atypical adenomatous hyperplasia, adenocarcinoma in situ, and invasive adenocarcinoma throughout the lung, as compared with parental Kras(G12D) mice, where STAT3 was not hyperactivated. Among IL6 family cytokines, only IL6 was upregulated in the lung. Accordingly, normalization of pulmonary STAT3 activity, by genetic ablation of either Il6 or Stat3, suppressed the extent of lung cancer in the model. Mechanistic investigations revealed elevation in the lung of soluble IL6 receptor (sIL6R), the key driver of IL6 trans-signaling, and blocking this mechanism via interventions with an anti-IL6R antibody or the inhibitor sgp130Fc ameliorated lung cancer pathogenesis. Clinically, expression of IL6 and sIL6R was increased significantly in human specimens of lung adenocarcinoma or patient serum. Our results offer a preclinical rationale to clinically evaluate IL6 trans-signaling as a therapeutic target for the treatment of KRAS-driven lung adenocarcinoma.
Association of age, baseline characteristics, co-morbidity and toxicity in castrate metastatic prostate cancer patients (CMPC) treated with chemotherapy
Authors: M. T. Fleming, K. W. Beekman, M. Warren, A. Wilton, G. Heller, H. Scher, W. K. Kelly
Journal: Journal of Clinical Oncology (2005)

4705 Background: Taxane (T) based chemotherapy improves survival in patients (pts) with progressive CMPC. A high frequency of non-cancer related factors places this group at risk for toxicities which can result in dose reductions and treatment delays that may compromise overall outcomes. We explored associations between age, baseline characteristics and co-morbidities and the ability to administer chemotherapy in CMPC. Methods: We evaluated the delivered chemotherapy to 108 sequentially treated men enrolled on clinical trials for progressive CMPC treated with T or Epothilone (E) based regimens. Multi-variate analysis was performed to determine the predictors of dose reduction, delay or discontinuation of therapy due to toxicity. Studied were: age, Charlson Co-Morbidity, stage at diagnosis, Gleason grade, Karnofsky performance status (KPS), extent of disease, and baseline biochemical parameters. Results: The median age was 68 (range 52–84), KPS: 90 (range 70–90); PSA 95 ng/ml (range .5–1923 ng/ml), HGB 12.7 g/dl (range 8.2–15.7g/dl), Gleason 8 (range 4–10) Tumor 3 (range 1–4) of whom 66 (61%) received a T, 42 (39%) E, and 19% had significant co-morbidities (cardiovascular, diabetes or gastrointestinal). For the overall group dose reductions were seen in 52%, delays in 56%, and 44% discontinued therapy prematurely after a median of 5 (range 1 to 16) cycles. Most common reason to delay or reduce chemotherapy was leukopenia in 31%, and neurotoxicity in 19%. Significant associations existed with dose reduction (P<0.0001), delay (P=0.0039) or discontinuation (P=0.0082) depending on either T or E administered. Initial M stage (P=0.03) and age (0.09) trended to predict for discontinuing therapy. There was no association between co-morbidities and other baseline parameters to predict dose reduction, delay or discontinuation of chemotherapy. Conclusions: Toxicities requiring dose modifications occur frequently in pts with progressive CMPC treated with T based chemotherapy. The toxicities were regimen specific, and did not appear to be related to co-morbidities in a patient group that met the eligibility criteria for Phase II clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
EFFECTS OF ALEGLITAZAR ON CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH STAGE 3 CHRONIC KIDNEY DISEASE AND TYPE II DIABETES
Authors: Klas Malmberg, Markolf Hanefeld, Luis Ruilope, A. Lincoff, Giancarlo Viberti, Nadejda Mudie, Teresa Urbanowska
Journal: Journal of the American College of Cardiology (2013)
Strategically Timing Inhibition of Phosphatidylinositol 3-Kinase to Maximize Therapeutic Index in Estrogen Receptor Alpha–Positive, <i>PIK3CA</i>-Mutant Breast Cancer
Authors: Wei Yang, Sarah R. Hosford, Lloye M. Dillon, Kevin Shee, Stephanie C. Liu, Jennifer R. Bean, Laurent Salphati, Jodie Pang, Xiaolin Zhang, Michelle A. Nannini, Eugene Demidenko, Darcy Bates, Lionel D. Lewis, Jonathan D. Marotti, Alan R. Eastman, Todd W. Miller
Journal: Clinical Cancer Research (2016)

Phosphatidylinositol 3-kinase (PI3K) inhibitors are being developed for the treatment of estrogen receptor α (ER)-positive breast cancer in combination with antiestrogens. Understanding the temporal response and pharmacodynamic effects of PI3K inhibition in ER(+) breast cancer will provide a rationale for treatment scheduling to maximize therapeutic index.Antiestrogen-sensitive and antiestrogen-resistant ER(+) human breast cancer cell lines and mice bearing PIK3CA-mutant xenografts were treated with the antiestrogen fulvestrant, the PI3K inhibitor GDC-0941 (pictilisib; varied doses/schedules that provided similar amounts of drug each week), or combinations. Cell viability, signaling pathway inhibition, proliferation, apoptosis, tumor volume, and GDC-0941 concentrations in plasma and tumors were temporally measured.Treatment with the combination of fulvestrant and GDC-0941, regardless of dose/schedule, was significantly more effective than that with single-agent treatments in fulvestrant-resistant tumors. Short-term, complete PI3K inhibition blocked cell growth in vitro more effectively than chronic, incomplete inhibition. Longer-term PI3K inhibition hypersensitized cells to growth factor signaling upon drug withdrawal. Different schedules of GDC-0941 elicited similar tumor responses. While weekly high-dose GDC-0941 with fulvestrant continuously suppressed PI3K signaling for 72 hours, inducing a bolus of apoptosis and inhibiting proliferation, PI3K reactivation upon GDC-0941 washout induced a proliferative burst. Fulvestrant with daily low-dose GDC-0941 metronomically suppressed PI3K for 6 to 9 hours/day, repeatedly inducing small amounts of apoptosis and temporarily inhibiting proliferation, followed by proliferative rebound compared with fulvestrant alone.Continuous and metronomic PI3K inhibition elicits robust anticancer effects in ER(+), PIK3CA-mutant breast cancer. Clinical exploration of alternate treatment schedules of PI3K inhibitors with antiestrogens is warranted. Clin Cancer Res; 22(9); 2250-60. ©2016 AACRSee related commentary by Toska and Baselga, p. 2099.
High epidermal growth factor receptor expression in metastatic lymph nodes may be more prognostic than in primary tumor for colorectal cancer survival
Authors: Y. Deng, B. F. Kurland, J. Wang, J. Bi, W. Li, P. Lan, T. Lin, E. H. Lin
Journal: Journal of Clinical Oncology (2008)

15031 Background: High epidermal growth factor receptor (EGFR) expression in the primary tumor is prognostic for poor survival in colorectal cancer (CRC). Discordance of EGFR expression has been noted in the paired primary versus nodal or distant metastasis. The aim of this study was to evaluate prognostic value of elevated EGFR expression in nodal or distant metastasis versus primary tumor tissue. Methods: Tissue microarrays from 93 surgically resected CRC primaries were analyzed for EGFR expression using immunohistochemistry along with 49 paired metastatic lymph nodes (MLN) and 19 distant metastases. Logistic regression, Kaplan-Meier survival curves, and the log-rank test were used to describe the association of tumor stage and survival with EGFR level dichotomized to low expression (0,1) versus high expression (2,3). Results: High EGFR expression in primary tumor, MLN and distant metastasis were 18%, 24%, and 21% respectively. In stage III/IV patients, eight of 14 patients (57%) with EGFR+ primary tumors did not show high expression in MLN, and 6/35 (17%) patients with EGFR- primary tumors gained high EGFR expression in MLN. High EGFR expression in primary tumor was associated with stage III/IV versus stage I/II disease (odds ratio 5.5, P = 0.012) and therefore predicted poor survival (P = 0.046). High EGFR expression in the primary or in distant metastasis was not associated with poor survival, whereas only high EGFR expression in MLN was associated with poor survival in stage III and stage IV disease combined or separately (Table 1) Conclusions: High EGFR expression in MLN appears more accurate in predicting survival than its expression in the primary or distant metastasis, thus may aid in selecting patients to receive adjuvant treatment incorporating anti-EGFR therapy. Prognostic values of discordant EGFR expression in different tissues warrants further investigation. Log rank P-values comparing overall survival for high EGFR expression in primary and metastatic tis Stage III/IV(n=49) Stage III(n=30) Stage IV(n=19) Pirmary tumor 0.332 0.795 0.161 Metastastic lymph node 0.005 0.002 0.014 Distant metastasis 0.246 No significant financial relationships to disclose.
Interaction of histologic type and grade in predicting survival from soft tissue sarcoma
Authors: R. J. Canter, R. J. Bold, A. S. Robbins
Journal: Journal of Clinical Oncology (2008)

10530 Background: Histologic grade has traditionally been considered the paramount prognostic factor in predicting survival for soft tissue sarcoma (STS). We hypothesized that histologic type modifies the prognostic effect of grade. Methods: Utilizing the population- based California Cancer Registry, we identified 8,740 cases of STS diagnosed between 1994 and 2003. Grade was categorized according to the ICD-O-3 five-level system (1 = well differentiated, 2 = moderately differentiated, 3 = poorly differentiated, 4 = undifferentiated/anaplastic, 9 = unknown). Using survival as the outcome variable, grade and histologic type were grouped into three categories, respectively, based on non- overlapping 95% confidence intervals (low, intermediate, and high for grade and favorable, neutral, and unfavorable for histologic type). Because there was a significant interaction between grade and histologic type, we examined the effect of grade within categories of histologic type, and the effect of histologic type within categories of grade. Five-year actuarial disease-specific survival was estimated using the Kaplan- Meier method. Results: Among 114 histologic types, malignant fibrous histiocytoma (20.8%), leiomyosarcoma NOS (12.4%), sarcoma NOS (7.0%), and myxoid liposarcoma (5.3%) were the most prevalent. Sixty-eight histologies were diagnosed in 20 patients or fewer (0.2%). Grade distribution was as follows: 1, 9.9%; 2, 15.1%; 3, 11.6%; 4, 23.8%; and 9, 39.6%. Five-year survival was 25.3% higher for patients with low versus high grade tumors (95.1% versus 69.8%). However, within each grade category, there was a statistically significant gradient of survival associated with histologic type. In the low grade category, survival was 20.2% higher for favorable versus unfavorable types (97.0% versus 76.8%). In the intermediate grade category, survival was 5.6% higher for favorable versus unfavorable types (91.4% versus 85.8%). In the high grade category, survival was 36.7% higher for favorable versus unfavorable types (89.3% versus 52.6%). Conclusions: Histologic type modifies the effect of grade in survival from STS. Within each grade category, there are significant differences in survival based on histologic type. Histologic type is an important predictor of biologic behavior in STS. No significant financial relationships to disclose.
Prevalence of Self-reported Symptoms After Gastric Bypass Surgery for Obesity
Authors: Sigrid Bjerge Gribsholt, Ane Mathilde Pedersen, Elisabeth Svensson, Reimar Wernich Thomsen, Bjørn Richelsen
Journal: JAMA Surgery (2016)

Population-based studies on the prevalence of symptoms after Roux-en-Y gastric bypass (RYGB) surgery are sparse. Knowledge about possible predictors of these symptoms is important for prevention.To examine patients' overall well-being and the prevalence and predictors of medical, nutritional, and surgical symptoms after RYGB surgery, and their association with quality of life.A survey was conducted from March 3 to July 31, 2014, among 2238 patients who underwent RYGB surgery between January 1, 2006, and December 31, 2011, in the Central Denmark Region. A comparison cohort of 89 individuals who were matched with patients according to sex and body mass index but who did not undergo RYGB surgery were surveyed as a point of reference. Data analysis was conducted from September 1, 2014, to June 25, 2015.Prevalence and severity (based on contacts with health care system, ranging from no contact to hospitalization) of self-reported symptoms following RYGB surgery. Prevalence ratios (PRs) of symptoms associated with different predictors were computed. The association between number of symptoms and quality of life was investigated using the Spearman rank correlation coefficient.Of 2238 patients undergoing RYGB surgery, 1429 (63.7%) responded to the survey. Among these patients, 1266 (88.6%) reported 1 or more symptoms a median of 4.7 years after RYGB surgery. Mean age at the time of the survey was 47.1 years (range, 26.9-68.0 years), and 286 were men (20.0%). A total of 1219 of 1394 patients (87.4%) reported that their well-being was improved after vs before RYGB surgery, while 113 (8.1%) reported reduced well-being. Symptoms after RYGB surgery were reported by 1266 patients (88.6%); 966 patients (67.6%) had been in contact with the health care system about their symptoms vs 31 [34.8%] of those in the comparison group, and 416 (29.1%) had been hospitalized vs 6 [6.7%] of those in the comparison group. The symptoms most commonly leading to health care contact after RYGB surgery were abdominal pain (489 [34.2%]), fatigue (488 [34.1%]), and anemia (396 [27.7%]). The risk of symptoms was higher among women (crude PR, 1.23; 95% CI, 1.11-1.37), among patients younger than 35 years (PR, 1.24; 95% CI, 1.13-1.36), among smokers (PR, 1.11; 95% CI, 1.02-1.20), among unemployed persons (PR, 1.15; 95% CI, 1.06-1.24), and in those with surgical symptoms before RYGB surgery (PR, 1.34; 95% CI, 1.25-1.43). Quality of life was inversely associated with the number of symptoms (r = -0.30; P < .001).Most patients reported improved well-being after RYGB surgery, but the prevalence of symptoms was high and nearly one-third of patients were hospitalized, 4- to 5-fold more than among the comparison group. Predictors of symptoms included young age, female sex, smoking, and experiencing symptoms before RYGB surgery. Development of weight loss procedures with fewer subsequent symptoms should be a high priority.
Donor leukocyte infusions for chronic myeloid leukemia relapsed after allogeneic bone marrow transplantation.
Authors: B M Bär, A Schattenberg, E J Mensink, A Geurts Van Kessel, T F Smetsers, G H Knops, E H Linders, T De Witte
Journal: Journal of Clinical Oncology (1993)

Treatment options for patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT) are limited. Treatment with lymphocytes from the original marrow donor and the influence on the malignant clone was studied in these patients.Seven patients with CML that had relapsed after BMT with T-cell-depleted grafts were treated. Six patients received leukocyte infusions from the original marrow donor. One patient received a second BMT with unseparated marrow from the same sibling donor. Chimerism was studied using erythrocyte and cytogenetic markers. Residual leukemic cells were monitored by cytogenetic analysis of the Philadelphia (Ph) chromosome and by polymerase chain reaction (PCR) of the breakpoint cluster region/Abelson (BCR-ABL) fusion gene.In five patients with hematologic relapse, the Ph chromosome disappeared 1 to 3 months after the leukocyte infusions. Cytogenetic analysis and in situ hybridization (ISH) showed only donor cells during further follow-up. Four to five patients became negative for the BCR-ABL translocation by PCR. Graft-versus-host disease (GVHD) always preceded response and was severe in two patients. One patient with cytogenetic relapse showed no response after leukocyte infusions. GVHD after second BMT was of moderate severity. One year after second BMT, PCR for the BCR-ABL translocation was negative.Infusion of donor leukocytes is an effective treatment with a low mortality in patients with CML relapsed after BMT with a T-cell-depleted graft. Longer follow-up and more patients will be needed to know whether cure will be permanent.
Prognosis of colorectal cancer with microsatellite instability
Authors: P. Benatti, M. Marino, R. Gafà, D. Barana, M. Pedroni, A. Scarselli, C. Di Gregorio, L. Roncucci, C. Oliani, G. Lanza, M. Ponz de Leon
Journal: Journal of Clinical Oncology (2005)

3548 Background: Microsatellite instability (MSI) characterizes almost all Hereditary Non-Polyposis Colorectal Cancer (HNPCC) cases and 10–15% of sporadic colorectal cancer (CRC). The clinical outcome of these tumors and the role of MSI as prognostic factor is still debated, in particular for what concerns the relationship between chemotherapy and MSI. In this study, we examined whether MSI in CRC could carry further prognostic information. Methods: One thousand and two hundred and fifty CRC patients(pts) were addressed to MSI testing in the context of a population-based biomolecular screening or for clinical suspicion of HNPCC in 3 different institutions. All the tumors were tested with 3 mononucleotide markers (BAT25, BAT26 and BAT40) and by immunohistochemistry: tumors were defined MSI+ when instability was present in at least two loci. CRC specific survival was analyzed with Kaplan-Meier method in relation to MSI, sex, age at diagnosis, stage, grading, cancer subsite, histological type, diagnosis of HNPCC according to the presence of MMR genes mutation, chemotherapy. The independent effect of each variable was then tested through Cox regression multivariate analysis. Furthermore the effect of chemotherapy in stage II and III CRC pts were analyzed both in MSI and microsatellite stable (MSS) CRCs. Results: Two hundreds and forty three pts, of whom 42 HNPCC, were affected by MSI+ CRC. At the end of the observation period, 788 were alive. Log-Rank test revealed stage, age, MSI+ and grading significantly related to survival. Cox regression model confirmed the effect of these prognostic factors. Considering stage II and III colorectal cancers only, MSI confirms its independently significant prognostic role: in particular, prognosis of MSI CRC pts does not seem influenced by the use of chemotherapy, thus confirming what recently reported. Finally the observation, in univariate analysis, of a better prognosis in HNPCC patients than in the sporadic MSI counterpart, could be attributed to the different stage and age at diagnosis in the 2 groups. Conclusions: MSI in this sample including pts with hereditary CRC appears as independent prognostic factor in colorectal tumors and could be of help in optimizing the appropriate strategy of therapy and follow up. No significant financial relationships to disclose.