tbuckley/cabot-search huggingface dataset:
Post-treatment [18F] fluorodeoxyglucose positron emission tomography as a prognostic tool for progression-free survival in epithelial ovarian cancer
Authors: H. Chung, J. Kim, N. Park, Y. Song, S. Kang, H. Lee
Journal: Journal of Clinical Oncology (2007)

16029 Background: The aim of this study was to evaluate response to therapy using post-treatment molecular imaging with [18F] fluorodeoxyglucose (FDG), and to compare the response with outcome in patients with epithelial ovarian cancer (EOC). Methods: This was a retrospective medical record review of 179 patients with EOC. All patients underwent post-treatment whole-body positron emission tomography (PET) imaging scan with [18F] FDG from August 1998 to April 2005. Patients were treated with surgical staging procedure followed by platinum-based combination chemotherapy at least 3 cycles. Post-treatment whole-body FDG-PET was performed 1 to 7 months (median, 3 months) after completion of treatment. Results: One hundred fourteen patients showed no abnormal FDG uptake while 65 patients had abnormal FDG uptake at the scan. One hundred thirteen patients experienced recurrence or metastasis during follow-up. Median progression-free survival (PFS) was 44 (range 2–83) months, and 5-year PFS rate was 34.3%. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of [18F] FDG PET images in the diagnosis of ovarian cancer recurrence or metastases were 46.1%, 82.8%, 59.2%, 82.8%, and 46.1%, respectively. A Cox proportional hazards model of survival outcome indicated that abnormal post-treatment FDG uptake (persistent or new) was the most significant prognostic factor for developing metastatic disease and death from EOC (hazard ratio, 0.432; 95% CI 0.296 to 0.630; P &lt;.0001). However, there was no relation between the maximal standardized uptake value (SUVmax) and the PFS. Conclusion: Post-treatment abnormal FDG uptake (persistent or new) detected by whole-body PET measures tumor response and might be predictive of poor prognostic ourtcome from EOC. No significant financial relationships to disclose.
Navelbine (NVB) oral (o) with cisplatin (CDDP) as induction and concomitant to radiotherapy (RT): Final results of an international phase II trial in stage III non-small cell lung cancer (NSCLC)
Authors: B. Utracka-Hutka, M. Krzakowski, M. Provencio, E. Villa, M. Codes, A. Kuten, M. Riggi, N. Caux, B. Longerey, B. Dubray
Journal: Journal of Clinical Oncology (2007)

7691 Background: NVB i.v. with CDDP has reported an optimal activity/tolerance ratio when used in combination with RT. The new oral formulation of NVB should be easier to use assuming a similar activity profile. An international phase II trial with NVBo + CDDP as induction followed by NVBo+CDDP+RT was implemented in order to evaluate the efficacy of this combination. Methods: Patients (pts) between 18 and 70 years, with histologically proven untreated locally advanced inoperable stage IIIA/IIIB (supraclavicular LN and pleural effusion excluded) NSCLC, adequate bone marrow, hepatic and renal function, KPS ≥ 80% were treated with NVBo D1,8 60 mg/m 2 cycle 1 and 80 mg/m 2 cycle 2 (if no haematological/non-haematological grade 3–4 toxicity) and CDDP 80 mg/m 2 every 3 weeks for 2 cycles as induction. OR/NC pts received NVBo D1,8 40 mg/m 2 and CDDP 80 mg/m 2 every 3 weeks for 2 more cycles and RT 66 Gy in 6.5 weeks. Results: Between 12/01 and 12/03 54 pts were enrolled; stages IIIA 48%, IIIB 52%; squamous 59%; median age 57 years (range 41;71), median KPS 100% (range 80; 100%) 7% pts ≥ 5% weight loss at baseline. RDI of NVBo/CDDP were 86%/93% and 97%/98% at induction and in combination with RT, respectively. Forty-one pts (76%) during induction increased NVBo from 60 to 80 mg/m 2 . Reasons for non- escalation: haematological 7 pts, non-haematological 2, mistake 4. After 2 cycles of CT induction, OR (ITT) in the 54 pts was 37%. Toxicity during induction: G3–4 Neutropenia (28%), febrile neutropenia (7%), G3 nausea (11%), G3–4 vomiting (9%), G3 anorexia (4%) G4 diarrhoea (2%); G3 constipation (2%). Forty-seven out of 54 pts received CT-RT. Median RT delivered dose: 66 Gy. Tolerance: 9% G3 Neutropenia; no G3/4 oesophagitis; 2% G3 radiation dermatitis. Late pulmonary fibrosis 1 pt. One month after CT-RT completion the overall RR (ITT) in the 54 pts was 54% (95% CI: 40%; 67%). Median PFS/OS: 12.5 (95% CI: 9.6; 16.4) /23.4 (95% CI: 17.6; 29.8) months, respectively. Conclusion: NVB Oral with CDDP is effective in stage IIIA/IIIB pts. The excellent tolerance profile allowed to complete the CT/RT treatment in 94% of pts. NVB oral is a new and promising option which facilitates the concomitant administration of CT/RT. [Table: see text]
Results of a randomized study of every three-week dosing (Q3W) of darbepoetin alfa for chemotherapy-induced anemia (CIA)
Authors: T. P. Rearden, V. Charu, B. Saidman, A. Ben-Jacob, G. R. Justice, A. S. Manaim, D. Tomita, G. Rossi
Journal: Journal of Clinical Oncology (2004)

8064 Background: Darbepoetin alfa (DA, Aranesp®) administered Q3W is effective for the treatment of CIA (Kotasek et al, 2003). NCCN guidelines recommend initiating erythropoietic therapy when hemoglobin (Hb) is < 11 g/dL with a suggested target Hb of 11 to 12 g/dL. This study was designed to evaluate the ability of DA to maintain Hb ≥ 10 g/dL in mildly anemic pts (early intervention) and pts who become moderately to severely anemic before treatment (late intervention). Methods: Pts with baseline Hb ≥ 10.5 and ≤ 12 g/dL were randomized 1:1 to early (DA 300 mcg Q3W) or late intervention (treated if Hb ≤ 10 g/dL with DA 300 mcg Q3W) groups for up to 23 weeks. The primary endpoint was the percentage of pts in each group with a Hb drop below 10 g/dL. Patient-reported outcomes included the FACT-Fatigue subscale. Proportion endpoints were calculated using Kaplan-Meier (KM) methods. Results: The study is fully enrolled with 204 pts. Data through week 17 for 201 evaluable pts (99 early and 102 late) were analyzed. Mean (SD) baseline Hb for early pts was 11.1 (0.7) g/dL and 11.2 (0.6) g/dL for late pts. There was a significant (P < 0.0001) difference between the K-M proportion (95% CL) of pts with a Hb drop < 10 g/dL: only 29% (19, 38) of early pts vs. 65% (55, 75) of late pts. During the study, early pts maintained average Hb within the NCCN target range while late pts required DA after a median (95% CL) of 4.5 (3, 6) weeks after randomization. Thus, late pts achieved the NCCN target range after an average of 2 DA doses. The KM proportion (95% CL) for transfusions was lower for early pts (14%; 7, 20) compared with late pts (22%; 13, 30). Early pts also performed better on the FACT-Fatigue. Conclusions: These results suggest that DA 300 mcg Q3W is well tolerated and effective in achieving and maintaining Hb levels at a target level of 11–12 g/dL. In addition, early intervention results in fewer transfusions and greater symptom improvement compared with late intervention. The availability of a Q3W schedule for erythropoietic therapy can simplify the management of anemia and provide benefits for CIA pts and their caregivers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen; PCHOMG Amgen Amgen; PCGOMG Amgen PCHOMG PCHOMG
Fractional exhaled nitric oxide in bronchiectasis
Authors: Young-Jae Cho, Hyo-Jeong Lim, Jong Sun Park, Sei Won Lee, Jae Ho Lee, Choon-Taek Lee, Ho Il Yoon
Journal: European Respiratory Journal (2012)

Fractional exhaled nitric oxide (FeNO) can be measured easily, rapidly, and noninvasively for assessment of airway inflammation, especially mediated by eosinophil, such as asthma. In bronchiectasis, the pathogenesis has been known as chronic airway inflammation and infection with abnormal airway dilatation; however, there are little studies to evaluate the clinical application of exhaled nitric oxide in bronchiectasis.  From March 2010 to September 2011, 30 patients with bronchiectasis diagnosed by chest high resolution CT performed FeNO, compared with various pulmonary diseases, including asthma (n=24), COPD (n=21) and other infectious diseases (n=25). All patients carried out eosinophil count with chemistry, simple radiograph, sputum examination and spirometry, if indicated.  FeNO (mean, ppb) in patients with bronchiectasis was 19.1, compared to 68.4, 31.7 and 18.9 in asthma, COPD and other infectious diseases, respectively. FeNO in bronchiectasis was significantly lower than asthma (P  FeNO in bronchiectasis was lower than other respiratory diseases, especially compared with asthma. Clinical application of FeNO to bronchiectasis might be considered in the subgroup by clinical situation.
Study of association between p53 mutation and tamoxifen therapy in women with hormone receptor positive invasive ductal cancer
Authors: R. Varadarajan, G. Das, B. Janarthanan, M. Desouki, S. Kulkarni, J. Geradts
Journal: Journal of Clinical Oncology (2006)

10630 Background: ERα promotes cell proliferation in breast tumors whereas p53 impedes cell cycle progression. We have reported direct link between these two opposing pathways. Our preclinical studies have demonstrated that ERα binds directly to p53 and negatively regulates its function and that anti estrogens disrupted the ERα- p53 interaction. Previous retrospective studies by us and others in advanced breast cancer patients had shown presence of wild type p53 in ER+ve breast tumors is associated with better response to endocrine therapy. Objective: To demonstrate women with hormonal receptor(ER) +ve non-metastatic invasive ductal cancer (IDC) with wild type p53 in the tumor tissue will have better DFS and/or OS with tamoxifen compared to those with abnormal p53. Methods: Tissue micro array (TMA) from archival tumor tissue of patients with IDC seen at Roswell Park Cancer Institute (RPCI) between 1992 and 2001 was made. The p53 status was assessed by IHC staining of the TMA, was considered positive (abnormal) if ≥10% nuclear staining was noted. Only those patients in TMA with the following criteria were included for this report; non-metastatic IDC treated at RPCI, patients who received adjuvant tamoxifen (for ER+ve tumors), p53 IHC data available. Results: 83 patients in the TMA with ER+ve tumors who were treated with tamoxifen met the study criteria to test our hypothesis. 35 patients with ER-ve tumors were analyzed to evaluate p53 effect unrelated to p53-ER interaction. Median follow up was 5 years. 16/83 (19%) ER+ve tumors and 11/35 (31%) ER-ve tumors had abnormal p53. 14 (17%) ER+ve and 11(31%) ER-ve patients experienced recurrence. 16(19%) ER+ve and 6(17%) ER-ve patients died (all causes) during the follow up period. Univariate analysis with respect to p53 for OS and DFS were undertaken. No significant OS or DFS difference were noted between patients with tumor tissue wild type and abnormal p53, for both ER+ve or ER-ve tumors. Conclusions: This study does not show any difference in outcome with tamoxifen therapy between tumors with wild type and abnormal p53. A Study with larger sample size involving sequence analysis and IHC is required to conclusively demonstrate the effect of the two common occurrences (ER+ve and abnormal p53) and tamoxifen. No significant financial relationships to disclose.
Prognostic significance of elevated pretreatment serum CA-125 in patients (pts) with epithelial ovarian cancer (CEO) treated with surgery and platinum/taxane-based chemotherapy
Authors: A. Prat, M. Parera, S. Peralta, P. Martínez, B. Adamo, M. Pérez-Benavente, A. Gil-Moreno, A. Garcia, J. Martínez- Palones, J. Baselga, J. del Campo
Journal: Journal of Clinical Oncology (2008)

22011 Background: The aim of our study was to investigate pretreatment serum CA-125 concentration as a prognostic factor in pts with EOC. Methods: A retrospective analysis was conducted on 219 pts treated at our institution between 1998–2007 for EOC with surgery and platinum/taxane-based chemotherapy (primary treatment). We analyzed the relationship between serum CA-125 values (>35 kU/l) and known prognostic factors (age, FIGO stage, residual disease [RD] after primary treatment, histology, and histological grade). The Wilcoxon-Mann-Whitney test was used to compare the CA-125 distributions across subgroups of patients depending on the previous covariates. Survival analysis was based on progression/recurrence using the Cox proportional hazards regression model. For this analysis, pts were divided into groups of equal numbers of pts with serum CA-125 levels of ≤100, 100–200, 201–400, 401–800, 801–2000, and >2001 kU/l. Results: Median CA-125 value=382.5 kU/l (range 36–50,400). Stage I-II=62 pts; stage III-IV=157 pts. Median follow-up=39 months (range 2–144). A significant correlation was found between age (p=0.0213), stage (p<0.0001), RD (p=0.0021), histological grade (p=0.0245), serous histology (p=0.0770) and serum CA-125 levels, respectively. In the multivariable analysis, the joint effect of preoperative CA-125 was significant for PFS (Hazard Ratio (HR) [95% CIs] for PFS=1.1938; p=0.0125). In addition, stage (HR=2.7491, p=0.0004), histological grade (HR=1.67, p=0.0366), and RD (HR=2.0517, p=0.0035) were also associated with PFS. Conclusions: Pre-primary treatment elevated serum CA-125 values are an independent prognostic factor for PFS in pts with EOC treated with surgery and platinum/taxane-based chemotherapy. This serum tumor marker is significantly associated with age, stage, histological grade, and residual disease after primary treatment. No significant financial relationships to disclose.
Secondary T790M mutation and novel G796A mutation in exon20 of EGFR gene in patients with non-small cell lung cancer who show resistance to gefitinib
Authors: H. Uramoto, K. Sugio, T. Oyama, T. Iwata, T. Onizuka, M. Yasuda, M. Sugaya, T. Nozoe, M. Takenoyama, T. Hanagiri, K. Yasumoto
Journal: Journal of Clinical Oncology (2007)

7703 Background: Somatically acquired mutations in the EGFR gene in non-small cell lung cancer are associated with a significant clinical response to a tyrosine kinase inhibitor (TKI). EGFR mutations occur predominantly in exon19 and/or exon21, namely, an in-frame deletion in exon19 or a missense mutation in exon21 (L858R), which have been found to be related to the sensitivity to TKI. However, most patients with such sensitive mutations in their tumor show progression during the TKI treatment. In such resistant tumors, a secondary threonine- to-methionine mutation at codon 790 (T790M) in exon20 has been reported to be related the resistance to either gefitinib or erlotinib. Methods: EGFR mutations in exons19–21 were examined by sequencing in 37 pretreatment tumors obtained from patients with NSCLC, who were treated by gefitinib. Of the 22 cases having sensitive EGFR mutations (19del or L858R), 15 showed CR/PR and 7 showed SD/PD. Of the 15 patients with CR/PR, 4 tumor samples (2 lung, 1 liver, and 1 pleural effusion) that became refractory to gefitinib, were obtained. In pretreatment tumor samples from 4 patients, an in-frame deletion of exon19 was observed in 3 tumors and a L858R mutation of exon21 was in 1 tumor. We next examined whether a secondary mutation occurred in a tumor with acquired resistance to gefitinib in 4 patients by the sequencing of exons 19–21, with informed consent. Results: Three of 4 tumor samples had a secondary T790M mutation, which was not detected in the pretreatment tumor samples. These 3 samples also had an in-frame deletion in exon19. There were no other novel secondary mutations in exons 19,20,21. In 7 cases showing resistance to gefitinib (SD/PD) in spite of the existence of sensitive mutations, 1 tumor demonstrated the co-existence of a missense mutation (G796A) in exon20. In vitro, a stable clone of cells bearing the G796A mutation was approximately 50,000-fold less sensitive to gefitinib in comparison to the cells carrying exon19 deletion. Conclusions: The T790M mutation is common in patients with acquired resistance to gefitinb. Our results suggest that screening tumor samples for a range of EGFR mutations may therefore improve our ability to identify the patients most likely to benefit from treatment with TKI. No significant financial relationships to disclose.
Comparison of Lynch predictive models for identification of MLH1/MSH2 mutation carriers in a Spanish multicentre clinic- based cohort
Authors: I. Valenzuela, J. Balmaña, M. Rue, I. Blanco, A. Torres, T. Ramon y Cajal, I. Chirivella, C. Guillen, J. Brunet, I. Tejada
Journal: Journal of Clinical Oncology (2009)

e22077 Background: Different predictive models for Lynch syndrome have recently been developed and their comparative performance in a clinic-based cohort has not been assessed. We aimed to analyze the accuracy of the MMRpro, Barnetson, and PREMM 1,2 models to predict MLH1/MSH2 mutation carrier status in 564 unrelated probands with clinical suspicion of hereditary colorectal cancer and compare it with Wijnen model and clinical criteria. Methods: Overall, 538 individuals (95%) underwent mismatch repair (MMR) deficiency screening before germline genetic testing (sequencing with or without large rearrangement analysis) and 26 (5%) performed direct genetic testing. Prediction scores for all individuals were calculated by each model. Sensitivity, specificity, positive predictive value (PPV), and the areas under the receiver operating characteristics curves (AUC) for all models were calculated and compared with the Revised Bethesda Guidelines (RBG). Results: 114 individuals (20%) were mutation carriers (63 MLH1, 51 MSH2). The AUC was 0.95 (95% CI: 0.93–0.97) for MMRpro, 0.87 (95% CI 0.83–0.91) for the Barnetson model, 0.87 (95% CI 0.83–0.91) for PREMM 1,2, and 0.75 (95% CI 0.69–0.80) for the Wijnen model (p&lt;0.001). Testing thresholds and specificity at 100% and 90% sensitivity for each model were: 0.001/17% and 0.33/89% for MMRpro, 0.01/9% and 0.07/59% for Barnetson, 0.05/5% and 0.11/58% for PREMM 1,2. Sensitivity and specificity of RBG were 86% and 14%, respectively. Calibration was 0.92, 1.05, 0.50, and 1.25 for PREMM 1,2, Barnetson, Wijnen, and MMRpro, respectively. Conclusions: In a population of individuals at risk of Lynch syndrome, the MMRpro model has the largest AUC, although the Barnetson and PREMM 1,2 model also show adequate discrimination. Any of the models perform better than the RBG and provide quantitative risk estimation of finding a MLH1/MSH2 mutation useful in genetic counselling. No significant financial relationships to disclose.
Factors for choosing prostate cancer treatment and resulting impact on health related quality of life
Authors: K. Rice, K. Peay, J. Hudak, S. Elsamanoudi, J. Travis, R. Lockhart, C. Jennifer, L. Black, S. Hogue, S. Brassell
Journal: Journal of Clinical Oncology (2009)

9601 Background: The equivalence of surgery (RP), external beam radiation (EBRT), and expectant management (EM) on overall survival of prostate cancer (PCa) patients and their respective impact on health-related quality of life (HRQoL) is controversial. Thus, the benefit of screening has been raised. There is a scarcity of information on demographic factors that influence patient treatment choice and the resulting impact treatment has on HRQoL. Methods: Patients presenting to an equal access military multi-disciplinary PCa clinic are enrolled in a HRQoL database after informed consent. Surveys are administered prior to treatment and at 3, 6, 9, and 12 months. The instruments are the EPIC, EPIC Demographic, and the MOS Short-Form 36. Chi-square analysis compared frequency of race, income, and education level by treatment choice. Multivariate analysis was used to predict changes in HRQoL outcomes over time. Results: The study consisted of 538 patients. Caucasians chose EM twice as frequently as African Americans (AA) (p=0.0033). Caucasians were 3 times more likely to choose RP over EBRT, whereas AA were more evenly divided. Patients who earned over $100,000 annually disproportionately chose RP while the other treatment groups were disproportionately represented by those earning less than $100,000 (p&lt;0.0001). Those having a graduate school degree disproportionately chose RP while the other treatment options were disproportionately represented in those with college education or less (p&lt;0.0001). Mean age for RP, EBRT, and EM was 58, 67, and 69 respectively. Patients undergoing RP had significantly worse HRQoL outcomes in the following domains: urinary function, sexual function, and sexual bother at 12 months despite having the highest baseline scores (p&lt;0.0001). The only domain that differed between patients undergoing EBRT and EM was bowel bother (p&lt;0.0001). Conclusions: Patients choosing RP tend to be younger Caucasians with higher income and educational levels. This cohort chose the option with the greatest impact on HRQoL, which gives evidence that patients with certain demographics may emphasize other factors in their treatment decisions. HRQoL between EBRT and EM differed in only one domain. EBRT may be offered to older patients with minimal HRQoL impact. No significant financial relationships to disclose.
Use of thermal sensation as a biomarker of response to palliative radiotherapy for cancer-induced bone pain.
Authors: A. C. Scott, B. J. Laird, H. I. Wan, S. M. Fleetwood-Walker, R. Mitchell, G. D. Murray, L. A. Colvin, M. T. Fallon
Journal: Journal of Clinical Oncology (2010)

9068 Background: Radiotherapy (XRT) is the gold standard treatment for cancer-induced bone pain (CIBP), but not all patients achieve adequate analgesia. The aim of this study was to identify predictors of response to XRT for CIBP, as currently no clinical biomarkers of response are known. Methods: The Brief Pain Inventory (BPI) and Quantitative Sensory Testing (QST) were completed before and 6-8 weeks after XRT for CIBP. Using warm (40°C) and cool (25°C) rollers in the CIBP and control sites, thermal sensation was tested. Analgesic response was defined as a reduction in BPI worst pain score of ≥30% at the CIBP site. Mann-Whitney test compared responders and non-responders and those with normal and abnormal sensation. Multivariate regression analysis examined potential predictors of response to XRT. Results: 42 patients were assessed pre and post XRT (16 male (38%), median (range) age 65.5 (38-88) years). Primary sites included breast (52%), prostate (29%) and lung (12%) with spine the most common site of CIBP. 29 patients (69%) responded to XRT. In responders, the number of patients with normal cool sensation increased from 3 (10%) pre XRT to 13 (45%) after XRT and fell in non-responders from 5 (38%) to 4 (31%). Number of patients with normal warm sensation increased from 6 (21%) to 14 (48%) in responders and decreased from 6 (46%) to 5 (38%) in non-responders. Median (range) reduction in worst pain (0-10 scale) in those with altered warm sensation was 3 (-2-10) vs. 1.5 (-2-5) in those with normal sensation (p=0.02). In those with altered cool sensation before XRT, worst pain score improved by 3 (-2-10) vs. 1.5 (-2-5) in those with normal sensation (p=0.03). For patients with altered warm and cool sensation the median (range) improvement was 3.5 (-2-10) vs. 2 (-2-5); p=0.01. Patients with reduced sensation to cool at baseline were more likely to respond to XRT (odds ratio 6.67, 95% CI 0.99-45). Abnormal cool sensation was independently predictive of response (p=0.03). Conclusions: Predicting analgesic response to XRT would enable individualized care, avoiding unnecessary treatment in a frail population with limited life expectancy. Thermal assessment could be incorporated easily into practice and warrants further investigation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer