tbuckley/cabot-search huggingface dataset:
Non-steroidal anti-inflammatory drugs and the risk of melanoma
Authors: J. M. Jeter, J. D. Bonner, T. Johnson, S. B. Gruber
Journal: Journal of Clinical Oncology (2005)

1027 Background: Non-steroidal anti-inflammatory medications (NSAIDs) have been shown to inhibit tumor growth in melanoma cell lines and mouse models of melanoma. We investigated the association between NSAIDs and melanoma in a case-control study comparing individuals with invasive melanoma, those with in situ melanoma, and melanoma-free controls. Methods: We recruited 327 subjects with incident melanoma diagnosed in 2000 (222 with invasive melanoma and 105 with in situ melanoma), as well as 117 melanoma-free spouse controls. All subjects completed a structured interview that assessed personal and family history of cancer, sun exposure, skin phenotype, and medication use. Current use of NSAIDs was assessed by subject self-report with a minimum duration of three months of daily use. Results: Use of NSAIDs, aspirin, and cyclo-oxygenase-2 (COX-2) inhibitors was reported by 7.66%, 9.23%, and 5.63% of subjects, respectively. The unadjusted odds ratio (OR) for use of any NSAID was 0.73 (95% CI 0.34–1.55) in a comparison of subjects with any melanoma to those without melanoma. After adjustment for age, sex, skin type, hair and eye color, and family history, the OR was 0.59 (95% CI 0.24 - 1.47). Similar results were found when restricting to cases with invasive melanoma (adjusted OR 0.64, 95% CI 0.27 - 1.73). Use of COX-2 inhibitors was also inversely related to any melanoma diagnosis (adjusted OR 0.44; 95% CI 0.14 - 1.35) and to invasive melanoma diagnosis (adjusted OR 0.58; 95% CI 0.18 - 1.9). Aspirin users had an unadjusted OR of 0.93 (95% CI 0.47–2.01), and an adjusted OR of 1.59 (95% CI 0.48–5.22). Conclusions: These results suggest that NSAIDs may be associated with a reduction in melanoma risk. This association, although not statistically significant, is consistent across classes of melanoma diagnosis and subtypes of NSAIDs. Because of potential overmatching of spouse controls, the odds ratios reported here are likely to be attenuated. Larger studies are required to evaluate potentially meaningful protective effects of NSAIDs. In addition, these findings need to be balanced with recent data showing that rofecoxib (a COX-2 inhibitor) increases the risk of cardiovascular events. No significant financial relationships to disclose.
A phase II trial of pemetrexed plus gemcitabine as first-line treatment for locally advanced or metastatic transitional cell carcinoma of the urothelium
Authors: H. von der Maase, J. Lehmann, G. Gravis, H. Joensuu, B. Bihn, P. Geertsen, J. Gough, Z. J. Chen
Journal: Journal of Clinical Oncology (2005)

4592
Results of a phase I study of RAD001 in combination with lenalidomide in patients with relapsed or refractory multiple myeloma.
Authors: A. K. Mahindra, P. G. Richardson, P. Hari, J. Laubach, I. M. Ghobrial, R. L. Schlossman, E. Weller, N. C. Munshi, K. C. Anderson, N. S. Raje
Journal: Journal of Clinical Oncology (2010)

8032 Background: Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or relapsed/refractory multiple myeloma (MM) patients following ≥1 prior therapy. RAD001, an mTOR inhibitor has been studied as a single agent in MM and had no significant single-agent activity, but was well tolerated. Predicated upon our previous preclinical studies demonstrating synergistic anti-MM activity of mTOR inhibitors when combined with Len, we evaluated this combination as a non-steroid containing oral regimen in advanced MM. Methods: Patients (pts) with relapsed and refractory MM were assigned to Len and RAD001 to be taken for 21 days of a 28 day cycle (NCT00729638). Pts were allowed to continue therapy until disease progression or unacceptable toxicity. Results: Twenty-eight pts were registered on the trial;2 pts were replaced for rapidly progressive disease or failure to meet eligibility criteria on day 1. Data on 26 pts are currently available. Both cohort 1 and 2 required expansion because of grade 3 neutropenia and grade 4 thrombocytopenia. Dose limiting toxicities included grade 4 neutropenia and thrombocytopenia in 2/3 pts in cohort 3 (Len: 20 mg and RAD001: 5 mg × 21 days). The maximum tolerated dose (MTD) was therefore declared at 15 mg of Len and 5 mg of RAD001 for 21 days with a 7 day rest period. Most common (≥10%) grade 1/2 events included nausea, fatigue, dyspnea, diarrhea, constipation, neuropathy and muscle cramps, all of which were manageable with supportive care. One pt developed RAD related non-infectious pneumonitis requiring discontinuation of therapy. Grade 3/4 adverse events ≥ 5% included thrombocytopenia (11%) and neutropenia (22%). Nineteen pts completed 2 cycles and are evaluable for response: 12 pts received treatment at MTD. Overall response rate including MR + PR was 63% (90% CI: [30.76%]), with 1 pt achieving SD. Conclusions: The combination of Len plus RAD001 is a well tolerated regimen with predictable hematological toxicities. The response rate to date has been encouraging in this heavily pretreated pt population. This combination provides an oral, steroid-sparing treatment strategy which warrants future evaluation in phase II studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Celgene, Millennium, Novartis Celgene, Millennium, Novartis AstraZeneca, Millennium, Novartis
The use of statins and the effect on survival in patients with small cell lung cancer
Authors: A. S. Hanbali, E. Urbaez Duran, D. Wang, M. Jankowski, A. Syed, S. Farhan, R. Chapman
Journal: Journal of Clinical Oncology (2006)

17121 Background: Hypercholesterolemia is one of the most common morbidities in United States. Statins have been proven as effective cholesterol-lowering agents and have been widely used in this country. They have been reported reducing the incidence and risk of various cancer types. However, the impact of using statins on the survival of patients with diagnosed small cell lung cancer is unknown. Methods: A retrospective study involved a cohort of 282 patients with diagnosed small cell lung cancer. Patients were identified from the Tumor Registry at Henry Ford Health System between January 1995 and December 2002. Electronic medical records of these patients were reviewed. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Out of 282 patients, there were 73 patients with hypercholesterolemia, 37 of them were statin users at the time of their small cell lung cancer diagnosis. Average age was 65 (range 34–87) years for non statin users and 69 (range 52–85) years for statin users. Median survival of 282 subjects was 7.37 months. After stratifying for statin use, the median survival of statin users was 8.66 months while the median survival of non statin users was 7.17 months (p = 0.29). Conclusion: Though slightly prolonged median survival in statin-users was observed, no survival benefit is demonstrated from this patient population. Factors that may have contributed to this result will be further discussed. With the trend of an increase in median survival among statin users, whenever possible, continuation of statins as co-morbidity management may still benefit patients with small cell lung cancer, during their receiving standard anti-tumor therapies. No significant financial relationships to disclose.
Iterative anesthesia for radiation therapy in pediatric oncology: Safety of a procedure using propofol alone.
Authors: H. Sebban, L. Claude, C. Conter, V. Bachelot, P. Marec Bérard, P. Bachmann, A. Daunizeau, C. De La Fouchardiere, C. Carrie
Journal: Journal of Clinical Oncology (2010)

9578 Background: Iterative anesthesia is sometimes mandatory to properly deliver radiotherapy in young children with malignant tumors. The safety of the anesthesic procedure is a crucial issue. Methods: Since 2002, we have been using for anesthesia a technical procedure associating propofol alone without any adjuncts and without any premedication for children less than five requiring radiotherapy for their tumours. This technic always requires a central venous access. Main contraindications are prone position for irradiation, concomittant bronchic infection, symptomatic cranial hypertension, neurological defect, deglutition troubles and gastro-oesophageal reflux. We analysed our cohort of patients in order to detect complications. Results: From 2004 to 2009, 53 children received this procedure representing a total of 617 sessions of radiotherapy. Median age was 2.5 years (range: 11 months to 5 years), there were 32 male. There were 19 neuroblastoma, 14 medulloblastoma or ependymoma, 12 rhabdomyosarcoma, 5 other sarcoma and 3 other tumours. Radiotherapy site were abdominal and/or pelvic in 25 pts, encephalic or head and neck in 25 pts, mediastinal field in 2 pts and leg in one patient. Median Propofol used for induction is 2.2 mg/kg (range:1.5-2.5). Propofol continuous infusion vary from 0.15 to 0.20 mg/kg/mn. Oxygen is provided by face mask. Pulse oxymetry, heart rate and capnography by nasal canulae. Two cameras able to zoom are focused one on the patient and another one on the monitor. The patient was transferred to recovery room between 60 to 90 minutes. Most of them are treated in an outpatient setting. There were no airway obstruction, no apnea, no hemodynamic changes except one case of desaturation requiring the discontinuation of the procedure. In 3 cases, the session had to be delayed of one day due to dysfunction of the central venous access.No evident long-term sequelae had been reported by the parents. Conclusions: Propofol alone is a safe procedure for iterative anesthesia when children undergoing radiotherapy are adequately selected by a multidisciplinary approach. No significant financial relationships to disclose.
E-cadherin expression in locally advanced (LAHNSCC) or metastatic head and neck carcinoma
Authors: E. Saada, F. Ettore, A. Sudaka, E. Chamorey, J. Sudaka, O. Dassonville, K. Benezery, G. Poissonnet, R. J. Bensadoun, M. Schneider, F. Peyrade
Journal: Journal of Clinical Oncology (2008)

6038 Background: Loss of E-Cadherin (E-Cad) function or expression has been associated with cell adhesion, cancer progression and metastasis. We conducted immunohistochemical correlative analyses to check for E-Cad influence on clinical outcome in locally advanced or metastatic head and neck squamous cell carcinomas (HNSCC). Treatment group 1 (TT1) included patients with LAHNSCC treated with surgery plus adjuvant radiochemotherapy. Treatment group 2 (TT2) included patients with LAHNSCC or metastatic disease treated by definitive radiochemotherapy or exclusive chemotherapy, respectively. Methods: This retrospective study included 142 patients treated in our center from 2000 to 2006. All patients received at least 2 cycles of cisplatin 75mg/m2 every 3 weeks. Demographic data (age at diagnosis, sex, tobacco use, alcohol consumption, status at last follow-up), tumor characteristics (stage, differentiation, primary site) and treatment data were collected. 2 experimented pathologists who were unaware of the clinical data independently evaluated E-Cad immunohistochemical expression. Survival univariate and multivariate analyses were performed using the log-Rank test and a Cox regression model, respectively. Results: Median follow-up was 23 months. Sex ratio was 4.9. 43 patients (30.3%) were in the TT1 group and 99 (69.7%) in the TT2 group. Overall survival was correlated to E-Cad median score according to Allred's method. On univariate analysis, the type of treatment (TTT1 vs TTT2), metastatic status and E-Cadherin expression were significantly predictive of overall survival (respectively, p<0.0001, p=0.005; p=0.01). Patients with low expression of E-Cadherin had significantly longer survival. However, E-Cadherin expression did not correlate with tumor stage, differentiation, primary site, tobacco smoking or type of recurrence. Conclusions: Unlike previous published data showing low E-Cadherin expression with poor outcome, our data suggest that high E-Cadherin expression may be associated with poor prognosis in LAHNSCC and metastatic HNSCC. These contradicting results warrant further investigations including specific studies in homogenous stage groups to better address the role of E-Cadherin in cancer progression. No significant financial relationships to disclose.
Effects of chromosomes 1, 3, 10 and 17 alterations on patient response to trastuzumab in metastatic breast cancer
Authors: S. S. Jewell, L. E. Morrison, L. Usha, B. A. Blondin, R. D. Rao, B. Tabesh, M. Kemper, M. Batus, J. S. Coon
Journal: Journal of Clinical Oncology (2005)

554 Background: Amplification of Her-2 (ERBB2) in breast cancer is linked to response to trastuzumab. However, response rates are only 20–40%, with amplified ERBB2, and more specific tumor profiling is needed. The region of chromosome 17 surrounding the ERBB2 locus is rich in genes with potential cancer relevance and their variable inclusion within the ERBB2 amplicon may profoundly affect response. The genomic status of components of the growth factor signaling pathway may also affect response. Methods: We used fluorescence in situ hybridization (FISH) to correlate genomic status of TOP2A, PTGS2, PIK3CA, AKT3, PTEN, 1q25 and the centromeres (cen) of chromosomes 3, 10, and 17 with response in metastatic ERBB2-amplified breast cancer treated with trastuzumab (alone or with non-anthracycline drugs). Average probe signals per cell, or ratios of probe signals were used to classify specimens as gained (>3 signals) or deleted (<1.5 signals), amplified (ratio>2) or not amplified (ratio<2), for respective loci. Contingency analysis was used to categorize response relative to genomic status, and p-values were calculated using Fisher’s exact test (2-sided; <0.05 considered significant). Results: Of the 35 patients with interpretable responses and FISH, 40% (14) had response (complete or partial) to therapy and 60% (21) were not responsive (stable or progressive disease). TOP2A amplification and normal copy number of PTGS2, 1q25, and cen 10 each adversely affected response. Most significant were classifications based on TOP2A [7.1% (1/14) response when amplified, 62% (13/21) when not amplified; p=0.0015], and 1q25 [14% (2/14) response when normal, 60% (12/20; p=0.013) when deleted or gained]. Targeting improved further when TOP2A and 1q25 status were combined [15% (3/20) response for amplified TOP2A and normal 1q25; 79% (11/14) for other; p=0.0003]. Conclusions: Measuring the genomic status of TOP2A and/or 1q25 may allow discrimination of patients very likely to respond to trastuzumab, versus those very unlikely to respond. A 4-color FISH assay containing ERBB2, cen 17, TOP2A, and 1q25 probes may improve considerably the ability to predict patients responsive to trastuzumab. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vysis Vysis
Cost-effectiveness of zoledronic acid vs. pamidronate in the management of hormone refractory prostate cancer (HRPC) patients with bone metastases
Authors: M. Botteman, V. Barghout, K. El Ouagari
Journal: Journal of Clinical Oncology (2006)

14660 Background: Canadian guidelines recommend zoledronic acid (ZA) (4 mg every 3 weeks) in patients with hormone HRPC and asymptomatic or minimally symptomatic bone metastases to reduce skeletal-related events (SRE). However, IV pamidronate (90 mg every 3 weeks) (PA) is also routinely used in this setting in spite of no significant improvement in occurrence of SRE or pain compared to NT. Objectives: To assess the cost effectiveness of ZA, PA, or no bisphosphonate therapy (NT) in the management of prostate cancer patients with bone metastases in Canada. Methods: A literature-based decision analytic model was developed to estimate the incremental cost and quality-adjusted life years (QALY) associated with the 3 treatment options. The model included assumptions about SREs, mortality, drug and administration costs, cost of SREs, reduced quality of life due to SRE and bone pain, and therapy duration. Sensitivity analyses considered several scenarios in which various assumptions were used regarding treatment efficacy and QALY gains due to pain relief and SRE prevention. All costs were expressed in Canadian dollars (2004). Results: The cumulative number of SREs over a patient’s remaining lifetime (1.9 years) was estimated at 2.69 for PA and NT patients and 1.76 for ZA. Total discounted costs were $11,918 for NT, $17,593 for PA, and $19,312 for ZA. Compared with patients receiving NT or PA, quality-adjusted survival increased by 0.094 (range depending on scenario considered: 0.072 to 0.106) QALY per patient for those on ZA compared to PA or NT. Compared to NT, ZA resulted in a cost per QALY gained of $78,366 (range: $50,717 to $101,831). Compared to PA, ZA resulted in a cost per QALY gained of $18,343 (range: $2917 to $23,835) per QALY gained. PA was more expensive than NT but did not improve patient-related outcomes. Conclusions: For HRPC patients with bone metastasis, zoledronic acid appears to be the only clinically valuable and economically acceptable option in Canada with a cost effectiveness likely better than previously reported. No significant financial relationships to disclose.
Elevated plasma TIMP-1 and survival in metastatic castration-resistant prostate cancer patients
Authors: W. K. Oh, K. Leitzel, S. Jacobus, R. Vargas, M. M. Regan, P. J. Hamer, W. P. Carney, S. M. Ali, P. W. Kantoff, A. Lipton
Journal: Journal of Clinical Oncology (2008)

11077 Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to have paradoxical multifunctional roles in tumorigenesis: inhibition of the catalytic activity of MMPs, growth promotion, inhibition of apoptosis, and regulation of angiogenesis. Increased TIMP-1 has been associated with an unfavorable prognosis in multiple cancers. Methods: EDTA plasma TIMP-1 was determined in 362 metastatic, castration-resistant prostate cancer (CRPC) patients using the TIMP-1 ELISA from Oncogene Science/Siemens Medical Solutions Diagnostics, Cambridge, MA. All patients with CRPC and available plasma were identified from a single institutional database and were studied in test (n=60) and validation (n=302) sets. Median follow-up from diagnosis was 5.8 and 6.6 years, respectively. Approximately 1/3 had received prior chemotherapy and 223 patients (62%) had died. Overall survival was analyzed using the Kaplan-Meier method and Cox modeling on plasma TIMP-1 tertiles. Results: Median plasma TIMP-1 levels were 335 and 183 ng/ml in the test and validation sets, respectively. Overall survival was significantly shorter with each higher tertile of TIMP-1 in both datasets (see table). In the validation set, multivariate analysis was performed with known prognostic factors in CRPC; TIMP-1, (high vs. low tertile, HR 2.4, p < 0.001), PSA (>20 vs ≤20 ng/ml), alkaline phosphatase (>102 vs. ≤ 102 U/L), ECOG PS (1+ vs 0) and Gleason score (≥8 vs <8) each remained significant covariates. Conclusions: Elevated plasma TIMP-1 levels predict decreased survival in metastatic CRPC patients, independent of known prognostic markers. Overall survival from the time of blood collection Test Set Validation Set Deaths/ Pts Median (mo) HR (95% CI),p vs. low Deaths/Pts Median (mo) HR (95% CI),p vs. low All patients 27/60 14 All patients 196/302 28 TIMP1 (ng/mL) TIMP1 (ng/mL) Low (<280) 7/20 22 1.0 Low (<159) 42/100 43 1.0 Medium 7/21 14 1.7 Medium 72/103 28 1.7 (1.2-2.5), (280-379) (0.6-4.8) (159-214) p=.007 High 13/19 6 4.5 (1.7-11.7), High 82/99 19 2.4 (1.7-3.5), (>380) p<.01 (>214) p<.001 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Oncogene Sciences/Siemens Siemens Oncogene Science/Siemens Oncogene Science/Siemens
Metastatic breast cancer and the elderly: A single institution, retrospective review.
Authors: Michael Kidd, Nina J. Karlin, Amylou C. Dueck
Journal: Journal of Clinical Oncology (2012)

55 Background: The aim of this retrospective study was to examine the overall survival (OS) of metastatic breast cancer patients over a decade and assess for any differences with respect to age, tumor characteristics, and ECOG status. Methods: Data on metastatic breast cancer cases from 1999-2010 were retrieved from the institutional cancer registry and linked to electronic medical records. Through chart review of 240 metastatic breast cancer cases, we determined hormone receptor (HR), HER2/neu (HER2), ECOG, age at diagnosis of metastatic cancer and mortality data. Kaplan-Meier survival curves for OS were used and compared between HR status, HER2 status, ECOG, and age at diagnosis using log-rank regression and Cox Regression analysis was performed to control for these variables. A 95% confidence interval (CI) was used. Results: The median OS of the sampled cases was 2.2 years (CI: 1.8-2.5 years). Analysis for overall survival by pre-determined age groups demonstrated no significant difference between the age groups (p value 0.46), but did yield a statistical difference based on ECOG status (p value 0.0001). Cox regression analysis showed consistent findings where survival was significantly affected by HR, HER2 status and ECOG but not age (HR: p value &lt;0.0001; HER2: p value 0.0132; ECOG: p value &lt;0.0001; age at diagnosis: p value 0.8462). Analysis for OS based on HR yielded a median survival of 1.4 years (CI: 0.9-1.6 years) for HR negative and 2.5 years (CI: 2.2-3.0 years) for HR positive (p value 0.0018). HER2 yielded a median survival of 1.8 years (CI: 1.4-2.3 years) for no amplification and 3.0 years (CI: 2.5 - 3.4 years) for amplification (p-value 0.0043). HR negative, HER2 non-amplified tumors had the poorest median OS at 0.7 years (CI: 0.5 - 1.1 years) whereas those tumors with HR positive, HER2 amplified had the best median OS at 3.0 years (CI: 2.5 - 4.7 years) with a p value &lt; 0.0001. Conclusions: In this retrospective analysis, there was no significant survival difference with respect to age. Age continued to have no significant effect on survival when adjusting for ECOG, hormone status, and HER2/neu status. Those factors that did act as determinants of survival were ECOG status, hormone status and HER2/neu status of the tumor.