tbuckley/cabot-search huggingface dataset:
Determining issues of importance for patients with lung cancer: Results of a web-based study in 660 patients with lung cancer to enhance the content validity of quality of life (QL) instruments
Authors: B. J. Davis, R. J. Gralla, P. J. Hollen, J. A. Petersen, R. B. Montgomery
Journal: Journal of Clinical Oncology (2008)

20518 Background: Identifying key issues for patients with cancer is central to assessing QL and patient reported outcomes (PROs), which aids in evaluating effectiveness of treatment programs for those with the disease. The first aim of this study was to enhance the content validity for the PRO instrument, the LCSS, by enlarging the patient panel (originally 121) with an additional 660 patients. These data can also be useful for any QL or symptom scale as well as helping to ascertain that programs address the needs expressed by patients. Methods: We used the established patient base of the web-based NexCura patient information resource to survey registered patients with lung cancer. Demographic stratifications included: stage of disease (metastatic 27%, locally advanced 37%, NED 36%); gender (55% women); KPS (≥80 = 46%, 70 = 28%, 60 = 16%); median age 62; NSCLC = 82%, SCLC = 18%; current treatment. 660 patients completed the anonymous web-conducted survey. Patients were asked to rank 20 issues on a 5-point scale assessing the importance of each item. Issues included general, lung-specific, psychosocial, spiritual and summative items. Results: The 9 highest ranked items are seen below; results are described by percent of patients choosing the top category (very important) and the top 2 rating categories of importance. Conclusions: Ratings by disease subsets (such as NED or M1 extent; by gender; by lung cancer type) were fairly similar to results found for the whole group, with the exception of the pain item being ranked second in those with stage IV extent. These results represent the largest survey of patient concerns in lung cancer and support using computer-assisted survey technology to assess such information in all malignancies to obtain patient input rapidly from large patient samples. These results give strong support for content validity for the LCSS and should be helpful in a variety of assessments in patients with lung cancer. Very Important Very Important + Important Good QL 80% 98% Maintaining independence 71% 97% Being a burden to others 65% 89% Perform normal activities 64% 96% Able to sleep 63% 94% Having pain 59% 86% Being fatigued 58% 93% Having shortness of breath 58% 89% Being depressed 47% 82% Lower ranked items (not shown): sexuality, GU, and spiritual issues; other symptoms Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration NexCura NexCura NexCura
Relationship of body mass index and other anthropometric measures and prostate specific antigen, NHANES 2001–2002
Authors: M. Saraiya, D. Werny, T. Thompson
Journal: Journal of Clinical Oncology (2006)

4649 Background: Obesity has been suggested to be a risk factor for prostate cancer. However, there has been limited information examining the relationship between body mass index (BMI) and other anthropometric measures such as triceps thickness (TT) and waist circumference (WC) and prostate specific antigen (PSA), a marker used in screening for prostate cancer. Methods: We analyzed data from the 2001–2002 National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of the non-institutionalized civilian US population. Participants in this study were limited to men aged 40 years and older without previously diagnosed prostate cancer (n = 1320). Weighted analyses were done overall and within three racial/ethnic groups [non-Hispanic whites (white), non-Hispanic blacks (black), or Mexican Americans (Mexican)]. BMI, TT, and WC were examined as both as a continuous and as a categorical variable. Three linear regression models were fit to determine the individual effect of BMI, TT, and WC on PSA within each racial/ethnic group after adjusting for age. Results: Among white men, the median PSA was 1.09 ng/mL [95% CI (0.96, 1.30)] for men with a normal BMI, 0.80 [95% CI (0.70, 0.94)] for overweight men, 0.83 [95% CI (0.74,0.95)] for obese men, and 0.74 [95% CI (0.56,1.22)] for severely obese men. Among black men, the median PSA for men was 0.83 [95% CI (0.70, 1.94)] and remained constant across BMI levels. Among Mexican men, the median PSA was 0.92 [95% CI (0.82, 1.23)] for men with a normal BMI, 0.91 [95% CI (0.81, 1.07) ] for overweight, 0.73 [95% CI (0.54,1.14)] for obese, and 0.59 [95% CI (0.39,1.06)] for severely obese men. In linear regression models controlling for age, a significant non-linear relationship was seen with BMI and PSA for both white (p = 0.010) and Mexican men (p &lt; 0.001) but not for black men (p = 0.167). Increased TT was associated with decreasing PSA for black and Mexican men. Increased WC was associated with decreasing PSA for white and Mexican men. Conclusion: These data do suggest racial/ethnic differences of PSA across BMI categories as well as other anthropometric measures. This finding may help inform practitioners about the relationship of anthropometric measures on PSA levels. No significant financial relationships to disclose.
Inhibition of angiogenesis and the growth of murine colon cancer with recombinant human endostatin adenovirus
Authors: Q. Li, L. Wang, Y. Wen, J. Zhou, L. Yang, Y. Wei
Journal: Journal of Clinical Oncology (2008)

14634 Background: Inhibition of angiogenesis is a promising approach to treat cancer. Endostatin, the COOH-terminal proteolytic fragment of the basement membrane component collagen XVIII, represents one of the most potent endogenous angiogenic inhibitors. Recombinant human endostatin adenoviruses (Ad-hE), encapsulated with (Ad-hE/Lipo) and without liposome, were evaluated for their potential anti-tumor activity. Methods: MTT colorimetric assay was used to evaluate the inhibition of endostatin on human umbilical vein endothelial cells (HUVECs). An in vitro model was established for the observation of angiogenesis using primary culture of CT26 tumor tissues. Mice bearing CT26 colon cancer either by subcutaneous or lung metastatsis, were treated with different concentrations of Ad-hE or Ad-hE/Lipo by intratumor or vena caudalis injection respectively. The level of endostatin in blood was tested using ELISA. In addition, the in vivo anti- angiogenesis effect was analyzed using either immunohistochemical CD31 staining on tumor tissues or alginate capsule models. TUNEL assay was also performed to study the potential effect of tumor apoptosis. Results: Endostatin was shown to inhibit the growth of HUVECs and the formation of blood vessels in the primary culture of CT26 tumor tissues. Sustained high level of serum endostatin was detected in mice treated with Ad-hE by intratumoral injection. By comparison, mice treated with Ad-hE via vena caudalis injection showed early but also rapid drop of endostatin in blood. Interestingly, mice treated with Ad-hE/Lipo showed more persistent level of endostatin than those treated with Ad-hE. Importantly, Ad-hE/Lipo treatment significantly reduced lung metastasis as compared to controls (p<0.01). Angiogenesis was apparently inhibited in tumor evidenced by immunohistochemical analysis and alginate encapsulation assay. The increased apoptosis was also found in tumor treated with Ad-hE or Ad-hE/Lipo as compared to the controls (p<0.05). Conclusions: Ad-hE and Ad-hE/Lipo effectively inhibited angiogenesis and tumor growth in murine colon cancer. The findings may provide a new vaccine strategy for cancer therapy. No significant financial relationships to disclose.
Use of bevacizumab after U.S. Food and Drug Administration (FDA) approval for first-line metastatic colorectal cancer (mCRC): A Cancer Outcomes Research &amp; Surveillance Consortium (CanCORS) study
Authors: Y. Zafar, S. C. Grambow, D. H. Abbott, D. Schrag, J. T. Kolimaga, L. Z. Conner, J. C. Weeks, D. Provenzale
Journal: Journal of Clinical Oncology (2008)

6562 Background: Bevacizumab improves survival in mCRC, but factors influencing its use subsequent to FDA approval in 2/2004 have not been identified. Methods: CanCORS is a multi-health system, prospective, cohort study including patients with incident colorectal cancer (CRC). Data were collected via patient interview and medical record review. Rates of bevacizumab delivery in first- line treatment of mCRC were determined via the medical record. Eligible patients for this analysis were diagnosed with stage IV disease and treated with first-line chemotherapy between 2/2004–1/2006. Medical records were abstracted for sociodemographics, stage, first treatment date, therapeutic agents delivered, and comorbidity. Of 3,311 incident CRC patients with complete record reviews, 605 (18%) had stage IV disease at diagnosis. Of these, 299 (49%) started initial chemotherapy after 2/2004, when bevacizumab was FDA-approved. Analysis focused on these 299 patients. Of the 299, 87% started first-line chemotherapy between 2/2004–2/2005. Logistic regression was used to evaluate factors associated with treatment. Results: 71% were male, 71% were ≤70 years, and 56% were Caucasian. Thirty-six percent had primary private insurance (non-private primary insurance included Veterans Administration, Medicare, none, and other). Using the Adult Comorbidity Evaluation-27 (ACE-27), 75% had no or mild comorbidity. Overall, 38% received bevacizumab, and 21% received first-line bevacizumab. Receipt of first-line bevacizumab was associated with having private insurance (odds ratio (OR) 2.72, p=0.01) and female gender (OR 2.23, p=0.02). No association was found between treatment with first-line bevacizumab and no/mild comorbidity (OR 2.01, p=0.06), age ≤70 (OR 1.53, p=0.26), and white race (OR 1.34, p=0.42). Conclusions: Over one-third of eligible patients received bevacizumab after FDA approval in 2/2004 and until 1/2006. Women and the privately insured were more likely to receive bevacizumab. Analyses of factors such as social support, employment status, and provider practice types are needed to further evaluate gender and insurance status differences in receipt of bevacizumab. No significant financial relationships to disclose.
Sequential capecitabine-based treatment of patients with metastatic colorectal cancer (MCRC) combined with oxaliplatin first-line: A retrospective analysis
Authors: H.-G. Hoeffkes, M. Arland, A. Freidank, O. Ranze
Journal: Journal of Clinical Oncology (2004)

3631 Background: A favorable outcome of first-line therapy of capecitabine (XEL) and oxaliplatin (XELOX) was recently documented for patients with MCRC. Retrospectively, we analyzed MCRC patients treated with sequential therapy of XELOX, XEL+irinotecan, and XEL+mitomycin in progressive disease (PD). Methods: Inclusion criteria: 18–75 yrs of age, serum creatinine < 1.5 mg/dL, informed consent. Therapy was capecitabine-based with 1,000 mg/m2 bid from day1–14 (XEL), first-line with oxaliplatin 130 mg/m2 (XELOX), d1 q3 wks for max of 6 cycles, if progress or toxicity, a second-line therapy with XEL and irinotecan 250 mg/m2 (XELIRI), d1 q3 wks for max of 6 cycles, if progress or toxicity, a third-line therapy with XEL and mitomycin 10 mg/m2 (XELMIC), d1 q3 wks for 6 cycles. CT scans performed every 12 wks to assess response according to the RECIST criteria. Primary objectives were the number of responses, time-to-progression (TTP), and overall survival. Secondary objectives were NCI-CTC Grad 3+4 toxicity. Results: All 16 pts, median age 61.2 yrs underwent prior tumor surgery. Sites of metastases were: liver (63%), lung (47%), peritoneum (33%), local (20%), others (33%). 7 pts (44%) received prior adjuvant chemotherapy. After a median of 5 cycles XELOX (range: 2–10) 1 CR (6%), 8 PR (50%), 3 SD (19%) and 4 PD (25%) were observed. In 1 pt XELOX dosage was reduced to 50% because of diarrhea. Median time of response was 13.1 wks (range: 0–26) with a median TTP (Kaplan-Meier estimation, 9 events, 7 censored) of 26 wks. 13 pts actually receive second-line XELIRI and 2 pts FOLFIRI. After 6 cycles of XELIRI, 4 pts have a PD and 1 pt a SD, yet receiving XELMIC. 3 pts died in week 29, 34 and 60 due to concomitant diseases. After a median of 33.4 wks (range: 20–60), 13 pts (81%) are still alive and median survival has not been reached yet. Grade 3 + 4 toxicity were: 6 diarrhea, 1 neutropenia, 1 hand-and-foot syndrome. Conclusions: First-line XELOX is safe and effective in MCRC with an overall response of 56% and a TTP of 28 weeks. Toxicities rarely occurred and are manageable with standard supportive care. No significant financial relationships to disclose.
Epidermal growth factor receptor (EGFR) mutation rate in advanced ovarian cancer (AOC): Results of a prospective study in Caucasian patients (pts)
Authors: A. Mustea, D. Koensgen, R. Zeillinger, D. C. Castillo-Tong, P. Sun, V. Mobus, J. Blohmer, C. Pirvulescu, W. Lichtenegger, J. Sehouli
Journal: Journal of Clinical Oncology (2006)

13127 Background: The EGFR is over expressed in 55% to 98% of advanced epithelial ovarian carcinoma. Different studies demonstrated EGFR status as an independent prognostic factor for OC. Recent studies in non small cell lung cancer suggest that the presence of the clinical response to tyrosine kinase inhibitors (e.g. ZD 1839) correlates with the somatic mutations in the kinase domain of EGFR, exons 18–21. For pts with OC data are not available on EGFR gene mutation. Methods: Shock-frozen samples from 32 patients (pts) with primary of ovarian cancer were stratified in two groups according to disease-free interval: ≤6 months (17 pts.) and &lt;6 months (15 pts.). All pts were prospectively collected within Tumor bank Ovarian Cancer Project. Patient collective consisted only from west European Caucasian women. Additionally, 9 commercial available ovarian cancer cell lines (TOV-90, TOV-112D, TOV-21G, OVCAR-3, A2780, A2780 ADR, ES-2, SK-OV-3, and Caov-3) and 32 established ovarian cancer lines were analysed. Exon sequencing of genomic DNA was used to detect L858R deletion mutations of EGFR within exons 21 of the kinase domain. PCR and capillary electrophoresis (Chip-Format) were used to analyse 15 bp deletion in Exon 19. We focused on descriptive analysis. The Log-Rank test was applied to confirm statistically significance (p-value of &lt;0.05). Results: Overall, 74.6% of the pts. were diagnosed FIGO stage III-IV. Median follow-up period was: 14.17 month (range: 2–42 months). Whether in cell lines, nor in tumor samples, stratified to response of platinum therapy any mutation of EGFR gene was observed. Conclusions: Our study indicates that the prevalence of mutation in the kinase domain of EGFR, exons 19 and 21 seems to be very low in pts. with AOC. Further studies should investigate other ethical groups of pts. No significant financial relationships to disclose.
Safety, pharmacokinetics and preliminary activity of the anti-IGF-IR antibody CP-751,871 in patients with sarcoma
Authors: D. Olmos, S. Okuno, S. M. Schuetze, M. L. Paccagnella, D. Yin, A. Gualberto, F. P. Worden, P. Haluska, J. S. De Bono, M. Scurr
Journal: Journal of Clinical Oncology (2008)

10501 Background: CP-751,871 is a fully human IgG2 monoclonal antibody against the insulin-like growth factor-I receptor (IGF-IR). Inhibition of the IGF-IR is a promising novel therapy for sarcoma. IGF-IR is implicated in autocrine and paracrine control of sarcoma, and IGF-IR blockade increases apoptosis and decreases migration, invasion, metastatic spread, and angiogenesis in sarcoma models. Methods: A cohort of patients (pts) ≥9 years of age with relapsed or refractory sarcoma, ECOG PS 0/1, and adequate hematological and biochemical function was opened with the primary objective of investigating the safety and tolerability of CP-751,871 in this pt population. Secondary objectives included evaluating pharmacokinetics and preliminary efficacy (RECIST). CP-751,871 was given by intravenous infusion at a dose of 20 mg/kg either q28 or q21 days. Results: Twenty-two pts were enrolled. Sarcoma subtypes treated were Ewing’s (n=9), synovial (n=5), desmoplastic small round cell tumors (DSRCT; n=3), rhabdomyosarcoma (n=2), fibrosarcoma (n=2), and chondrosarcoma (n=1). Median pt age was 35 years (range 12–63); 64% had ECOG PS 1. Median number of previous regimens was 3 (range 1–5). Pts received a median of 2 treatment cycles (range 1–16). Grade ≥3 treatment-related adverse events (CTCAE v3.0) reported included grade 4 uric acid increase (1 pt) and grade 3 bilateral deep-vein thrombosis (1 pt). Pharmacokinetics of CP-751,871 in sarcoma pts were comparable to those in other pt populations, with a half-life supporting the q21 or q28 day dosing regimen. Among 19 pts evaluable for response, one partial response was observed in a 12-year-old pt with Ewing’s sarcoma. Disease stabilization >3 months was observed in 6 pts (1 fibrosarcoma, 1 chondrosarcoma, 1 DSRCT, 1 synovial and 2 Ewing’s sarcoma pts). Six pts remain on study. Conclusions: CP-751,871 was well tolerated in pts with relapsed and/or refractory sarcoma. Preliminary activity in Ewing’s sarcoma warrants further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology ImClone Systems Incorporated, Pfizer Oncology, sanofi-aventis Pfizer Oncology ImClone Systems Incorporated, sanofi-aventis Novartis, Pfizer Oncology, sanofi-aventis
The impact of cancer on vulnerability in older Medicare beneficiaries
Authors: S. G. Mohile, Y. Xian, I. Lazurenko, G. R. Morrow, S. G. Fisher, W. Hall
Journal: Journal of Clinical Oncology (2008)

9578 Background: Vulnerable elders have a high prevalence of comorbidity, disability, or geriatric syndromes that place them at increased risk for decline or death. The impact of cancer as a predictor of vulnerability has not been well described. Methods: We analyzed a nationally representative sample of 12,480 community-based elders sampled in the 2003 Medicare Current Beneficiary Survey (MCBS). Differences in prevalence of comorbidity, disability, and geriatric syndromes between those with and without cancer were estimated. We also evaluated the differences in scores on the Vulnerable Elders Survey-13 (VES-13), a screening tool that predicted an increased risk for decline or death in an earlier MCBS cohort. Multivariate logistic regressions were utilized to identify independent predictors of functional deficit, abnormal VES-13 score, and geriatric syndromes. Results: Cancer was reported by 2349 (18%) pts. Among cancer pts, 32% had a deficit in activities of daily living (ADL), 49% had an instrumental ADL deficit (IADL), 64% had a significant comorbidity, and 68% had at least one geriatric syndrome. Cancer pts had significantly higher prevalences of functional deficit, comorbidity, and geriatric syndromes than those without cancer (all p values <0.0001). Mean score on the VES-13 was higher in cancer pts (p<0.0001). Adjusting for possible confounders including age and comorbidity, pts with any diagnosis of cancer were more likely to have an ADL deficit (OR 1.32, 95% CI: 1.18- 1.48), abnormal VES-13 score (OR 1.17, 95% CI: 1.04–1.31), or geriatric syndrome (OR 1.21, 95% CI: 1.08–1.34). When including specific cancer subtypes as dependent variables: lung, bladder, and ovarian cancer were independent predictors of ADL deficit; lung cancer predicted a high score on VES-13; colon, prostate, and bladder cancer predicted geriatric syndromes. Health care utilization and costs were highest among vulnerable (i.e., VES-13 ≥ 3) cancer pts than any other subgroup. Conclusions: Cancer pts have higher vulnerability than those without cancer. Defining the connections between cancer and vulnerability would identify targets for improving cancer care and quality of life in older people. Further research should describe the role of screening tools such as the VES-13 in predicting decline or death in elders with cancer. No significant financial relationships to disclose.
A phase II study of a combination of pemetrexed (Pem) and gemcitabine (Gem) in patients with metastatic breast cancer (MBC): An NCCTG study
Authors: C. X. Ma, P. Steen, K. M. Rowland, R. D. Niedringhaus, J. W. Kugler, J. N. Ingle, E. A. Perez, A. A. Adjei
Journal: Journal of Clinical Oncology (2004)

639 Background: Pem inhibits folate-dependent enzymes involved in thymidine and purine synthesis, has broad clinical activity, and exhibits synergistic cytotoxicity with Gem in preclinical models. We conducted a phase II study to assess the efficacy and toxicity of this combination in MBC. Methods: Eligible patients (pts) must have had an anthracycline and a taxane in either adjuvant or metastatic setting with no more than 1 chemotherapy regimen for metastatic disease (unless a taxane and anthracycline). Pts received Gem 1250 mg/m2 (IV; d1, 8) and P 500 mg/m2 (IV; d8) q21 days. Results: Fifty-nine pts were enrolled with median age of 51 (range 32–74), prior adjuvant chemotherapy regimens 0 (5 pts, 8%) or 1 (54 pts, 92%), prior metastatic chemotherapy regimens 0 (23 pts, 39%), 1 (35 pts, 59%), or 2 (1 pt, 2%). Twenty-eight (48%) had received prior hormonal therapy. Pts received treatments for a median of 5 cycles (range: 1–21) with median follow-up of 426 days. Considering grade 3 and 4 toxicities, 48 (81%) pts had neutropenia (gr 3: 11, gr 4: 37), but only 7 (12%) had febrile neutropenia. Fifteen pts (25%) had thrombocytopenia (gr 3: 13, gr 4: 2). Grade 3+ non-hematologic toxicity included 10 (17%) pts with dyspnea, 10 (17%) with fatigue, 4 (7%) with rash, 3 (5%) with nausea, and 3 (5%) with anorexia. Overall, 14 (24%; 95% CI: 16–39%) pts achieved PR with a median duration of at least 5 months. Nine (15%) had SD for ≥ 6 months with a median of 334 days (range 205–786). Median time to progression was 3.8 months (95% CI 2.6–5.7). Median survival was 10.3 months (95% CI 8.4–26.4) and the 1-year survival rate was 49% (95% CI 37–64%). Conclusions: The combination of Pem and Gem has activity and produces clinical benefit (CR + PR + SD ≥ 6 months) in 39% of pts with MBC who have previously been treated with an anthracycline and a taxane. No significant financial relationships to disclose.
Mutant Kras And Braf Gene Expression Profiles In Colorectal Cancer: Results Of The Translational Study On The Petacc 3-Eortc 40993-Sakk 60-00 Trial
Authors: S Tejpar, Vlad Popovici, M Delorenzi, Eva Budinská, H Estrella, Maria Leonor Limao Oliveira, S Weinrich, P Yan, Cutsem E Van, A Roth
Journal: Annals of Oncology (2010)