tbuckley/cabot-search huggingface dataset:
Sex as a predictive factor in metastatic colorectal cancer treated with bevacizumab containing chemotherapy.
Authors: Jae-Heon Jeong, Sun Kyung Baek, Jung Min Chae, Gil Yeon Lee, Sun Jin Park, Si-Young Kim, Hwi Joong Yoon, Kyung Sam Cho
Journal: Journal of Clinical Oncology (2012)

e14128 Background: Recently, bevacizuamb induced hypertension was suggested as being a predictive factor for bevacizumab in metastatic colorectal cancer (mCRC) patients. However, there wasn’t any useful pretreatment predictive factor for bevacizumab in our clinic. So, in this study, we investigated the predictive factors for bevacizumab in mCRC. Methods: From 2002 to 2011, thirty mCRC patients received bevacizumab containing chemotherapy in Kyung HeeUniversity Hospital, Seoul. Among them, 27 patients had a measurable disease which adequate for response evaluation using Response Evaluation Criteria for Solid Tumors. We analyzed predictive factors for bevacizumabin these 27 patients using chi-squaretest and binary logistic regression analysis. Results: Median age was 57.0. Thirteen patients (48.1%) were male. ECOG performance status was 0,1,2 (29.6%/59.3%/11.1%). Eight patients had right side tumor and nineteen patients had left sided tumor. Fifteen patients had two metastatic sites. Sixteen patients received bevacizumab containing chemotherapy as first or second line treatment. Fourteen patients received oxaliplatin based chemotherapy with bevacizumab. We analyzed predictive factors for bevacizumab containing chemotherapy. In the univariate analysis, response rate was higher (53.8% vs 14.3%) in male patients (p= 0.092, Fisher’s exact test). In the multivariate analysis (binary logistic regression analysis), gender was a significant predictive factor (p=0.046). Progression-free survival was 6.3 months (CI 95% :2.14 – 10.46 months) and 5.2 months (CI 95% : 3.92 –6.49 months) in male and female patients, respectively (log-rank, p=0.503). Overall survival was 9.4 months (CI 95% :7.2 – 11.63 months) and 11.7 months (CI 95% :10.3 – 13.08 months) in male and female patients, respectively (log-rank, p=0.773). Conclusions: Although sex is not a modifiable predictive factor, it appears that sex is an important predictive factor in metastatic colorectal cancer patients treated with bevacizumab containing chemotherapy.
Phase III study comparing cisplatin/vinorelbine plus cetuximab versus cisplatin/vinorelbine as first-line treatment for patients with epidermal growth factor (EGFR)-expressing advanced non-small cell lung cancer (NSCLC) (FLEX)
Authors: J. Von Pawel, K. Park, J. R. Pereira, A. Szczesna, C. Yu, V. L. Ganul, M. Krzakowski, J. K. Roh, K. Pilz, R. Pirker
Journal: Journal of Clinical Oncology (2006)

7109 Background: Cisplatin plus vinorelbine is a commonly used regimen for first-line therapy of advanced NSCLC, achieving response rates of 20–30% and median survival times of 6 to 11 months (mths). An earlier phase II trial investigated cetuximab in combination with cisplatin and vinorelbine in this setting and found improved response rates in the cetuximab arm, warranting this larger phase III trial. Methods: Patients (pts) with EGFR-expressing advanced NSCLC (stage IIIB with documented malignant pleural effusion and stage IV) were randomized 1:1 either to Group A (cetuximab 400 mg/m 2 initial dose then 250 mg/m 2 weekly, cisplatin 80 mg/m 2 on day 1, vinorelbine 30 mg/m 2 on day 1 and 8) or to Group B (cisplatin and vinorelbine as before) for a maximum of 6 three-weekly cycles. Cetuximab was administered until progression or unacceptable toxicity. Primary endpoint is overall survival time; secondary endpoints are progression-free-survival, tumor response, disease control, safety, and quality of life. Enrollment of 1,100 pts was planned to show an increase of median survival time of 25% with 90% power. The Data Safety Monitoring Board (DSMB) performed an independent preplanned safety analysis from the first 370 pts. Patients were followed for a minimum of 6 weeks (2 cycles). Results: Since November 2004, 1,037 pts have been randomized, 689 are under treatment, and 348 pts have discontinued the study. Demographics of the first 370 pts reflected known advanced NSCLC characteristics: 91% stage IV, median age 60 yrs (31–79), 38% female, 80% ECOG PS 0/1, 52% adenocarcinoma, 30% squamous cell carcinoma; 29% never-smokers, 17% Asian. The ten most frequent adverse events were: nausea, neutropenia, vomiting, anorexia, fatigue, constipation, anemia, febrile neutropenia, rash, and diarrhoea. Conclusions: The trial continued after review of all relevant baseline and safety information from the first 370 pts. Recruitment is ongoing. [Table: see text]
Prognostic impact of the 21-gene recurrence score (RS) on disease-free and overall survival of node-positive, ER-positive breast cancer patients (pts) treated with adjuvant chemotherapy: Results from NSABP B-28.
Authors: Eleftherios P. Mamounas, Gong Tang, Soonmyung Paik, Frederick L. Baehner, Qing Liu, Jong-Hyeon Jeong, Seong-Rim Kim, Steven M Butler, Farid Jamshidian, Diana B. Cherbavaz, Steven Shak, Thomas B. Julian, Barry C. Lembersky, D. Lawrence Wickerham, Joseph P. Costantino, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

1 Background: RS predicts outcome in node- and node+, ER+ pts treated with adjuvant endocrine therapy as well as benefit from adjuvant chemotherapy, with high RS receiving most of the benefit. We studied the prognostic impact of RS in node+, ER+ pts treated with adjuvant chemotherapy plus endocrine therapy as part of the NSABP B-28 trial. Methods: B-28 compared doxorubicin/cyclophosphamide (ACX4) with ACX4 followed by paclitaxel X4. Pts &gt;50 yrs and those&lt;50 yrs with ER+ and/or PR+ tumors also received 5 yrs of tamoxifen concurrently with chemotherapy. Between 8/95 and 5/98 3060 pts were accrued. The present study includes 1,065 pts ER+ by central tissue microarray IHC assay, tamoxifen treated, assessed by RS. Median follow-up time was 11.2 yrs. Results: Of the 1,065 pts, 386 (36%) had low RS&lt;18; 364 (34%) intermediate RS,18-30; and 315 (30%) high RS≥31. In univariate analyses RS was a significant predictor of DFS, distant recurrence-free interval (DRFI) and OS (Table). In multivariate analyses, RS provided independent prognostic information for all three endpoints beyond clinical and pathologic factors, e.g., treatment, age, tumor size, tumor grade, number of + nodes and type of surgery (p&lt;0.001). Conclusions: The 21-gene RS maintains significant prognostic impact in ER+, node+ pts who have received anthracycline- or anthracycline/taxane-based adjuvant chemotherapy. These findings emphasize the need to target pts with high residual risk for recurrence with additional therapies to overcome unfavorable biology, potential endocrine and/or chemotherapy resistance. Supported by: NCI, HHS, PHS, grants U10-CA-12027, -69651, -37377, -69974, and U24-CA-114732, and grants from Susan G. Komen for the Cure and Bristol-Myers Squibb Pharmaceutical Research Institute. [Table: see text]
The age-related increase in renal clusterin mRNA is accelerated in obese Zucker rats.
Authors: N J Laping, B A Olson, J R Day, B M Brickson, L C Contino, B G Short, S M Ali, D P Brooks
Journal: Journal of the American Society of Nephrology (1998)

Clusterin is a multifunctional glycoprotein associated with development and tissue injury. Because renal function decreases with advancing age in the obese Zucker rat, clusterin mRNA expression was examined in the kidney of young adult Zucker rats and compared with age-related changes in renal clusterin mRNA expression in Fischer 344 (F344) rats. Renal clusterin mRNA levels in the obese Zucker rat were 2.5-fold higher by 3 mo of age and fourfold higher at 5 mo of age compared with the lean strain. In comparison, renal clusterin mRNA in 12-mo-old F344 rats was twofold higher than in 3-mo-old animals and was tenfold higher at 24 mo of age. Clusterin mRNA was positively correlated with urinary protein excretion and negatively correlated with creatinine clearance in Zucker rats. Clusterin was increased in select nephrons of the obese Zucker rat kidney and in 24-mo-old F344 rat kidney as assessed by in situ hybridization. Increased expression of clusterin mRNA occurred mostly in the tubular epithelium of dilated, convoluted proximal tubules. These data indicate that renal clusterin mRNA levels increase as a function of age and that age-related increases in renal clusterin and the associated tubular abnormalities are accelerated in obese Zucker rats.
Fungus-fighting vaccine
Authors: Nicole Johnston
Journal: The Journal of Experimental Medicine (2005)

Fungus-fighting vaccineOn page 597, Torosantucci and colleagues describe a novel vaccine with the potential to confer protection against multiple fungal pathogens.In mice, the vaccine induced protective immunity against Candida albicans and Aspergillus fumigatus , both common fungal pathogens that prey on immunocompromised individuals.Vaccination generates anti-␤-glucan antibodies that inhibit Candida hyphae.
Risk factors of recurrent medullary thyroid cancer and factors that influence on prognosis
Authors: Y. H. Lee, H. Y. Park, J. H. Jung, K. H. Hwang
Journal: Journal of Clinical Oncology (2005)

5594 Background: Medullary thyroid cancer, which is quite a rare disease that occupies 5 - 10% of total thyroid cancers. Residual or recurrent MTC, manifested by elevated calcitonin levels, occurs commonly following a primary treatment of MTC. Methods: The study group consisted of 37 patients of MTC at Kyungpook National University Hospital between 1985 and July 2003. We analyzed the medical records of MTC operation cases in retrospective ways to find out treatment results and utilized the Kaplan-Meier and chi- square test to figure out the correlation of prognosis and recurrence. Results: The average age of patients was 39.4 years and 7 cases among them had a family history and accompanying disease. No one had metastasis at the time of diagnosis. 24 cases (64.9%) showed unilateral locations. 21.6% of them were diagnosed to be MTC in tests taken before operation and cold thyroid nodules were shown in 32 cases. Calcitonine was measured in 11 cases before operation took place, showing 2438 pg/ml on average and decreased in 10 cases after the operation. 48.6% of them showed lymph node metastasis at the time of operation and invasion of surrounding organs was shown in 13.5% of them. Total thyroidectomy and central neck dissection was carried out in all cases. Modified radical neck dissection was carried out at first in 17 cases. 13 cases out of 37 experienced a recurrence, and most was the neck recurrence. Treatment for neck recurrence was a modified neck dissection. 5 of them died and it was mostly due to lung metastasis. We analyzed the factors that affected recurrence and it was shown that lymph node metastasis and the TNM stage had a statistically significant relationship. No factor showed relevance to prognosis with multivariate analysis. The survival rates were 93.6% for 5 years, 86.1% for 10 years, and 76.5% for 15 years. Conclusions: We could not find any statistical significance in the factor relevant to prognosis in the patients in multivariate analysis. However, as the survival rate was 76.5% for 15 years, if surgical treatment (total thyroidectomy and central neck dissection) and constant follow-up are followed after operation, then future improvement can be expected from treatment for medullary thyroid cancer. No significant financial relationships to disclose.
Prognostic value of immunohistochemical stain pattern for carcinoembryonic antigen in patients with completely resected pathologic stage I lung adenocarcinoma
Authors: H. Suzuki, H. Matsuguma, S. Igarashi, R. Nakahara, Y. Ishikawa, T. Kondo, Y. Kamiyama, K. Mori, K. Tetsuro, K. Yokoi
Journal: Journal of Clinical Oncology (2008)

7553 Background: Surgery alone remains the standard therapy for patients with stage I NSCLC based on the recent results of randomized control trials. There is, however, a subgroup of patients with stage I disease who have a poor prognosis, for whom adjuvant chemotherapy can be as effective as that for patients with more advanced disease. Preoperative serum CEA level has been reported to be an independent prognostic factor for stage I NSCLC. Nevertheless, adjuvant therapy is not performed based on the serum CEA level, because it can be influenced by smoking or other lung conditions. Therefore, a more definitive indicator is considered necessary. We hypothesized that immunohistochemical (IHC) CEA expression would be a more reliable and effective prognostic marker than serum CEA levels. Methods: Between 1986 and 2000, 219 patients who underwent complete resection at our hospital were diagnosed as having stage I lung adenocarcinoma. Immunohistochemical staining with the antibody for CEA was carried out on paraffin embedded sections of those tumors using the avidin-biotin- peroxidase complex method. Preoperative serum CEA levels and other clinicopathologic factors were also investigated by univariate and multivariate analysis. Results: IHC CEA was positive in 186 patients (85%). The membrane pattern, in which only the cell membrane was stained, was observed in 92 patients; the cytoplasmic pattern (CP), in which cytoplasm was diffusely stained, was observed in 94 patients; and a negative stain pattern was shown in 33 patients. We combined the cell membrane pattern and negative stain pattern as the non- cytoplasmic pattern (NCP) on the basis of survival analysis. Survival analysis demonstrated that CEA IHC patterns and serum CEA levels as well as age and blood vessels invasion were significant prognostic factors on both univariate and multivariate analysis. The 5-year survival for patients with a high serum CEA level and CP was only 38%, compared to 79% for normal serum CEA levels and CP, 78% for high serum CEA levels and NCP, and 93% for normal serum CEA levels and NCP. Conclusions: Both CEA IHC patterns and serum CEA levels were independent prognostic factors for patients with pathologic stage I lung adenocarcinoma. No significant financial relationships to disclose.
Frameless Cyberknife radiosurgery for metastatic and primary brain tumors
Authors: E. T. Wong, X. Lu, J. Devulapalli, A. Mahadevan
Journal: Journal of Clinical Oncology (2006)

11527 Background: Cyberknife delivers image-guided stereotactic radiation to intracranial and extracranial skull base tumors without a frame. This frameless feature makes Cyberknife a completely non-invasive procedure and allows non-surgical neuro-oncology personnel to treat patients with tumors in the neuraxis. Methods: Patients with intracranial tumors were selected from our Brain Tumor Clinic if they were not surgical candidates or had residual tumors after neurosurgery. The decision for Cyberknife radiosurgery was made after careful review of all available treatment options in our multidisciplinary brain tumor conference based on patients’ history and neurologic findings, neuroimaging data, and pathology. All patients signed informed consent prior to fusion head MRI and CT scanning. They were pre-medicated with 4 mg of dexamethasone and 500 mg of levetiracetam twice daily. All dose plans were calculated based on CT images acquired from 1.25-mm slices with an inverse planning technique. Dynamic tracking software monitored patient movements and adjusted the robotic arm accordingly, compensating for patient motion up to 10 mm in translation and 5 degree in rotation. Results: Nine subjects with 15 treatment targets, including 4 meningiomas, 1 high-grade glioma, 1 plasmacytoma, and 3 melanomas, were treated with single-fraction or 5 fractions of Cyberknife radiosurgery. No acute toxicity was seen during or within 24 hours of treatment. One subject developed subacute onset of cerebral edema 2 weeks after the procedure but his symptoms were quickly reversed with dexamethasone. Conclusions: Cyberknife radiosurgery is a well-tolerated procedure for intracranial and extracranial tumors in the skull base. Neuro-oncologist, with the appropriate training, could perform Cyberknife radiation planning with radiation oncologists and physicists. No significant financial relationships to disclose.
Soluble factors (SF) associated with efficacy and toxicity of pazopanib (PZB) in advanced soft tissue sarcoma (STS) patients (pts): An EORTC-STBSG study.
Authors: S. Sleijfer, M. M. Van Glabbeke, C. Lamers, H. Burger, J. Blay, A. l. Cesne, M. R. Scurr, A. N. Bartlett-Pandite, S. Marreaud, P. Hohenberger
Journal: Journal of Clinical Oncology (2010)

10040 Background: PZB has interesting activity in relapsed non-adipocytic STS in a phase II (EORTC 62043; JCO 27(19):3126-32). We explored whether SF levels were related to outcome and toxicity. Methods: By a multiplex assay, 25 different serum SF were measured at baseline in 85 pts and also sVEGFR2 and PlGF at week 12 in 32 pts. Primary objectives were to explore associations between baseline SF levels and progression-free survival at week 12 (PFS12wks) (study primary endpoint) and between sVEGFR2 decrease and PlGF increase at week 12, both indicating VEGFR inhibition, and the PZB-specific toxicities hypertension and hypopigmentation. Secondary objectives were correlations with other efficacy end points and toxicities. Standard statistical tests were used. Results: At baseline, positive correlations were found for IL12p40 and MPC3 with PFS12wks, bNGF and HGF with PFS, and ICAM1 and IL2ra with overall survival (OS) (all p<.05). However, due to repetitive testing, false discovery rates were high (±20% for PFS and OS, 50% for PFS12wks). At 12 weeks, sVEGFR2 had decreased (1.1-2.7x) and PlGF increased (1-43x), both factors were strongly interrelated (p<.0001). Low sVEGFR2 and high PlGF levels at week 12 were associated with higher grade hypertension (p<.0005 and p<.002, respectively), but not with hypopigmentation. Associations were also observed with TSH elevations and poorer PFS12wks, and OS (all p<.05). Conclusions: Several baseline SF were related to outcome parameters, but these exploratory results should be interpreted with caution given high false discovery rates. Consistent with VEGFR inhibition, PZB decreases sVEGFR2 and increases PlGF levels, both are associated with the PZB-specific toxicities hypertension and TSH elevations. The association of these changes with poorer efficacy is unexpected and may point out alternative mechanisms of action of PZB in addition to VEGFR inhibition. Findings of this study will be validated in the currently ongoing phase III study of PZB in non-adipocytic STS. If confirmed, these factors may be used as early markers for response to PZB enabling further individualization of STS treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Largest series of extrapulmonary small cell carcinoma (ESCC): The Saskatchewan Experience
Authors: K. Haider, D. Finch, A. Sami, I. Ahmad, D. Mirchandani, R. Alvi, S. Yadav, S. Ahmed
Journal: Journal of Clinical Oncology (2004)

9681 Background: : Although ESCC has been recognized as a rare and distinct clinicopathologic entity, limited data is available about its clinical behavior and outcome. Our experience with ESCC over the past 3 decades is presented here. Methods: : Patients with ESCC were identified using Saskatchewan Cancer Registry - Canada, from 1971–2002. Diagnosis was based on immunohistochemistry and/or morphology. Patients with abnormal chest radiology at diagnosis or with well-differentiated neuroendocrine tumor or Merkel cell carcinoma were excluded. Survival was calculated using the Kaplan-Meier method. Results: A total of 101 eligible patients with ESCC were identified. Median age was 72 yrs (24–100) and M:F was 1.4:1. Median duration of symptoms prior to definitive diagnosis was 2 months [m] (0.25–40). 51 patients had localized disease and 50 had extensive disease.No significant difference was noted in age, gender distribution, comorbid illness, and incidence of of secondary cancer, however 96% of patients with limited disease (LD) had ECOG performance status of ≤2 compared with 52% in extensive disease (ED) [p=<0.0001]. The primary disease sites were as follows: Breast n=9; gastrointestinal n=20, genitourinary n=18, gynecologic n=11, head & neck n=10, thymus n=2, and unknown primary n=31 . Ninety percent of patients with LD received treatment and 98% of them had an objective response (OR). In contrast, 54% patients with ED received therapy and 44% of them had OR(p<0.0001). Median progression/relapse free survival in responding patients with LD was 20+ m (2–276) compared with 12+ m (2–68) in ED (p<0.0001). All the patients with LD had median OS of 34+ m (0.2–276) compared with 2+ m (0.1–108) in patients with ED (p<0.0001). 5 year survival in patients with LD was 31% compared with 2% in patients with ED. Conclusions: Our results reveal that natural history of ESCC seems comparable to small cell carcinoma of lung and that extent of disease is an important factor predicting survival. No significant financial relationships to disclose.
Extent of nodal dissection and patient age impact recurrence-free survival (RFS) after surgery for non-small cell lung cancer (NSCLC)
Authors: G. K. Dy, P. K. Dy, P. C. Chua, G. D. Nelson, N. R. Foster, S. Mandrekar, J. R. Jett, P. Yang, C. Deschamps
Journal: Journal of Clinical Oncology (2007)

7613 Background: Factors influencing the pattern of disease relapse after curative surgical resection in early stage NSCLC is unknown. We sought to evaluate the effect of tumor- and patient-related characteristics on the pattern of disease recurrence (local relapse and/or metastatic disease) and survival in relation to surgical resection for NSCLC. Methods: A consecutive retrospective series of 488 patients seen at Mayo Clinic Rochester who had complete resection of NSCLC between 1997 and 1998 was utilized. Cox proportional hazards model was used to evaluate the effect of age, gender, smoking status, TNM stage, number of lymph node (LN) involved, number of LN resected, and histopathologic diagnosis on RFS. Logistic regression was used to evaluate the effect on recurrence or death within the first 2 years after surgical resection. Results: Data on 342 patients with a median follow-up of 85 months (range: 0.1 to 162) are reported. 60% were male, and 81% had N0 stage at diagnosis. There were 26 (7.6%) never smokers. Median number of LN resected was 20 (interquartile range [IQR]: 14–29). Median age at surgery was 71 years (IQR: 64 to 76). A bi-modal pattern of local recurrence (N=62) after surgery for early stage NSCLC was observed, with 57% of patients having a local recurrence within 2 years and 21% of patients having a local recurrence from 5–7 years post-surgery. The median duration from surgery to first documented recurrence was 16 months (IQR: 8 to 39). While age, N stage, number of LN involved, and T stage were significant predictors of RFS univariately, only lesser LN resected (p=0.008), older age (p&lt;0.0001) and higher T-stage (p=0.003) were significant adverse predictors of RFS in the multivariate analysis when adjusted for all factors. Higher T-Stage was associated with a significantly increased risk of recurrence or death within the first 2 years after surgical resection (p =0.004). Updated results using data from all 488 patients will be presented in the meeting. Conclusions: A trend towards a bimodal distribution of local recurrences after surgical resection of early stage NSCLC was observed. Increased number of LN resected, younger age and lower T stage were associated with better RFS. No significant financial relationships to disclose.