tbuckley/cabot-search huggingface dataset:
Reproducibility of computed tomography (CT) measurements of lung cancer
Authors: L. P. James, B. Zhao, C. S. Moskowitz, G. J. Riely, V. A. Miller, P. Guo, M. S. Ginsberg, M. G. Kris, L. H. Schwartz
Journal: Journal of Clinical Oncology (2008)

8002 Background: The CT scan is the most widely used assessment of response to treatment for lung tumors. However, little is known about the reproducibility of the measurements obtained. Prior studies evaluated many lesions which were < 1 cm or which were not malignant. Since treatment decisions are based on measurements which may differ by as little as a few millimeters, we sought to systematically evaluate the degree of variation of CT scans of pulmonary lesions. Because tumors are not perfect spheres, volumetric assessments may more accurately measure tumor size and thus be more reproducible. Methods: 32 patients were enrolled. Inclusion criteria required a pathologically confirmed non-small cell lung cancer and primary tumor ≥ 1 cm. Patients first underwent a clinically indicated scan and then were immediately repositioned, at which time a second scan was obtained. Masses were segmented and measured using a semi-automated computer algorithm. Uni-dimensional (UNI), bi-dimensional (BI), and volumetric (VOL) data were analyzed using descriptive statistics. To measure reproducibility, the concordance correlation coefficient was calculated (Lin, 1989) and the conditional standard deviations (SD) for the second scans were determined. With 32 subjects, there was at least 80% power to find a coefficient > 0.75 using a two sided 0.05 level test. A range of ± 2 SD, corresponding to 95%, represents second measurements that could be reasonably expected given the first measurement. A hypothetical tumor 2 cm in diameter was used to illustrate the data set. Results: Data appear in the Table below. Conclusions: The ± 2 SD ranges reveal an extremely wide variation of measurements of a single tumor and come surprisingly close to current criteria of tumor response and disease progression. Because of its greater reproducibility (as seen by the concordance coefficient closest to 1.0), VOL has the potential for earlier and more accurate determination of increases in tumor size. Method Range of % difference Concord. coeff. 2 cm diameter example Tumor size ± 2 SD ± % difference UNI -8.5%, 8.3% 0.9981 2.00 cm 1.88, 2.13 -6.0%, 6.5% BI -16.8%, 20.0% 0.9965 3.14 cm2 2.62, 3.76 -16.6%, 19.8% VOL -19.3%, 10.3% 0.9995 4.19 cm3 3.69, 4.47 -11.9%, 13.6% No significant financial relationships to disclose.
Self -Reported Quality of Life in users and non-users of dietary supplements in cancer
Authors: J. Granick, J. A. Cambron, D. Gupta, A. Aslam, T. Wodek, J. F. Grutsch, C. G. Lis
Journal: Journal of Clinical Oncology (2005)

8232 Background: Hospital-based surveys suggest that cancer patients routinely use dietary supplements, which include vitamins, minerals, and herbs. We described the QoL characteristics of users of dietary supplements versus non-users. Methods: A survey of 225 adult cancer patients presenting for treatment at Cancer Treatment Centers of America at Midwestern Regional Medical Center was completed between 11/01 and 10/03. A validated instrument (McCune Questionnaire) assessed the use of 56 dietary supplements in the past month. QoL was evaluated using the EORTC QLQ-C30 questionnaire. The mean QoL scores were compared between the dietary supplement users and non-users using linear regression models controlling for tumor site. Results: Of 225 patients, 91 (40%) were males and 134 (60%) females. 136 (57%) patients had failed prior treatment while 65 (29%) were newly diagnosed. 67 (30%) had breast cancer, 40 (18%) colorectal cancer, and 32 (14%) lung cancer. 164 (73%) had used dietary supplements in the past month while 61 (27%) had not. Patients with colorectal and breast cancer had statistically significantly better QoL as compared to those with lung cancer for most EORTC scales. Mean EORTC QoL scores were significantly better among the dietary supplement users for physical and emotional function scales and fatigue, nausea, appetite loss, and constipation symptom scales after adjusting for tumor site (Table 1). Conclusions: Contrary to some of the previously published research this study found better QoL among the users of dietary supplements, as compared to non-users. The next step in this research is to prospectively evaluate the patterns of changing QoL in relation to dietary supplement use across the entire duration of cancer diagnosis and treatment. Table 1. Relationship between dietary supplement use and QoL after adjusting for tumor site No significant financial relationships to disclose.
A prognostic nomogram for predicting recurrence and survival in rectal cancers without neoadjuvant treatment.
Authors: Junjie Peng, Ying Ding, Hongbin Wu, Sanjun Cai
Journal: Journal of Clinical Oncology (2014)

555 Background: To develop a prognostic nomogram for predicting recurrence and survival in patients with locally advanced rectal cancers that were not able to receive preoperative treatment. Methods: A total of 887 patients with AJCC (7th edition) stage II-III rectal cancers were retrospectively collected from a single institution. All patients did not receive any preoperative treatment before curative resection of the primary tumor. Cox proportional hazards model was performed to develop the predictive model for OS. Results: The 5-year local recurrence rate, distant metastases rate, and overall survival rate were 22.2%, 32.9%, and 63.9%, respectively. A prognostic nomogram was successfully developed to predicting patients’ 5-year overall survival, with a concordance index of 0.7. Factors in this model included patients’ age, gender, CEA value, tumor location, T stage, N stage, metastatic lymph nodes ratio, lymphvascular invasion, perineural invasion, adjuvant chemotherapy, adjuvant chemoradiotherapy. Our nomogram improved the predicting accuracy of current AJCC stage system (7th edition). Conclusions: The prognostic nomogram integrated patients demographic and clinicopathologic factors, which is better able to account for tumor and patient heterogeneity. Our individualized prediction nomogram could help physicians counsel and advise patients about their personalized treatment strategies and follow-up protocols. [Table: see text]
Circulating protein and cellular biomarkers of sunitinib in patients with advanced neuroendocrine tumors.
Authors: A. J. Zurita, J. Heymach, M. Khajavi, L. Tye, X. Huang, M. Kulke, H. Lenz, N. J. Meropol, W. Carley, S. E. DePrimo, C. S. Harmon
Journal: Journal of Clinical Oncology (2011)

4079 Background: Biomarkers of sunitinib malate (SU) therapy were characterized via analysis of levels of a panel of soluble proteins in plasma samples collected from pts with advanced carcinoid and pancreatic neuroendocrine tumor (NET) treated in a phase II trial. Changes in specific subsets of peripheral blood mononuclear cells (PBMC) and circulating endothelial/progenitor cells (CEC/CEP) expressing relevant targets were also examined. Methods: Pts with carcinoid or pancreatic NET were treated with SU in 42-day cycles of 50 mg/day for 4 weeks followed by 2 weeks off treatment. Plasma levels of vascular endothelial growth factor-A (VEGF), soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, and interleukin (IL)-8 were analyzed by quantitative ELISA at baseline and on days 1 and 28 of cycles 1–4 and correlated with mature PFS and OS data. In a subset of pts (n=17), monocytes (CD14+) and CEC/CEPs were serially evaluated by fluorescence-activated cell sorting, and SDF-1α (n=28) was analyzed by ELISA. Expression on PBMC of receptor tyrosine kinases (RTKs) including VEGFR-1, PDGFR-β, and KIT was analyzed, along with CXCR4, CD34, and Tie-2 expression. CEC were defined as CD45-CD31+/CD146+ and CEP were defined as CD133+. Results: Baseline plasma sVEGFR-2 and SDF-1α levels were elevated in pts with pancreatic NET (n=41) compared with carcinoid tumor (n=66). SU treatment increased plasma VEGF and IL-8 and decreased plasma sVEGFR-2/-3. In pts with carcinoid tumors, pts with < median baseline levels of sVEGFR-3 and IL-8 had significantly prolonged PFS and OS. Although most white blood cell subsets decreased during treatment, monocytes were predominantly affected, particularly those expressing VEGFR-1. In addition, decreases in CEP and CXCR4+ monocytes correlated with IL-8 levels, whereas CEC correlated with sVEGFR-2/-3 levels. Conclusions: Low plasma sVEGFR-3 and IL-8 at baseline were associated with improved outcome (PFS and OS) in carcinoid pts. SU led to a preferential decrease in CD14+ PBMC subpopulations, particularly those bearing VEGFR-1. A novel simultaneous profiling of RTK-expressing PBMCs, CEC, and plasma angiogenesis-related factors may lead to the identification of biomarkers for SU activity.
The analytic validation of prostate-specific mRNA detection in whole blood by RT-PCR as a prognostic biomarker for patients with castration-resistant prostate cancer (CRPC).
Authors: Daniel Costin Danila, Aseem Anand, Glenn Heller, Mingliang Wan, Matthew Zehnder, Raya Khanin, Nikolaus Schultz, Martin Fleisher, Hans Lilja, Howard I. Scher
Journal: Journal of Clinical Oncology (2012)

36 Background: To estimate the association between molecular biomarkers and outcomes, robust assays are needed before clinical qualification. Although tumor specific transcripts detected in blood by PCR have been associated with outcome, an analytically validated platform enabling detection of CTC-associated transcripts in clinical settings remains to be identified. Here we explore the efficacy of detecting a panel of prostate specific transcripts in CRPC. Methods: Blood was collected from 97 pts with progressive CRPC in PAXgene tubes (2.5 ml) for total RNA extraction using PAXgene Blood RNA Kit. Five genes expressed in prostate but not in nucleated blood cells were analyzed by RT-PCR. We used Fluidigm Dynamic Array platform to analytically validate RT-PCR assays for KLK3, KLK2, HOXB13, GHRL2, and FOXA1 transcripts. Each PCR-reaction was run in 6 replicates, detection thresholds for each gene were chosen by ROC analysis of an independent set of 56 CRPC patients versus 51 healthy volunteers, and results were reported as transcripts present or absent. CellSearch reported CTC number/7.5 ml of blood drawn into CellSave tube. Results: Prostate specific transcripts (≥ 2 genes) were detected in 52/97 (54%, 95% CI 43-64%) of patients with progressive CRPC studied with a median survival time of 17 months (95% CI: 13.8, 23.5). 40/45 CRPC-patients with ≥ 5 CTC and 15/52 CRPC patients with &lt; 5 CTC had transcripts present in blood. Similar to CTC enumeration, transcript detection predicted overall survival in proportional hazards models that included LDH dichotomized at above and below 300. The predictive accuracy (CPE) of PCR detection + LDH was 0.785 (SE 0.036), comparable to CTC-enumeration + LDH (0.796, SE 0.035). Conclusions: Detecting prostate specific mRNA in whole blood using validated RT-PCR assays, applicable to larger CRPC cohorts, provides prognostic biomarkers that predict overall survival. The clinical utility in monitoring treatment will be prospectively explored. [Table: see text]
Clinical impact of expanded <i>BRAF</i> mutational status on the outcome for metastatic colorectal cancer patients with anti-EGFR antibody: An analysis of the BREAC trial (Biomarker Research for Anti-EGFR Monoclonal Antibodies by Comprehensive Cancer Genomics).
Authors: Kentaro Yamazaki, Takayuki Yoshino, Katsuya Tsuchihara, Eiji Shinozaki, Kei Muro, Tomohiro Nishina, Kensei Yamaguchi, Kiwamu Akagi, Satoshi Yuki, Takeharu Yamanaka, Shogo Nomura, Satoshi Fujii, Hiroyasu Esumi, Yukiko Abe, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2015)

573 Background: BRAF V600E mutation has been recognized as a prognostic marker in patients (pts) with metastatic colorectal cancer (mCRC). Several studies have consistently shown a significant association between the presence of BRAF V600E mutation and resistance to anti-EGFR antibody therapy in pts with previously treated mCRC while there are few reports on the clinical impact of minor BRAF mutations. Methods: The BREAC trial was a multicenter, retrospective study to investigate the novel biomarkers of anti-EGFR antibody therapy. RAS and BRAF mutations were detected by targeted sequencing using FFPE materials of mCRC pts who received anti-EGFR antibody after a failure to standard therapies. Progression-free survival (PFS), overall survival (OS), and response rate (RR) were evaluated according to expanded RAS/BRAF mutational status. Results: Of 184 pts enrolled in the study, RAS/BRAF testing was succeeded in 150 pts. Patients characteristics were as follows; male/female 87/63, median age 63.5 years (range, 28-85), PS 0/1/2 81/65/4. Median PFS, OS, and RR were 4.0 months, 12.4 months, and 21%, respectively. Expanded RAS and BRAF mutations were detected in 40 pts (26.7%, KRAS/NRAS 29/11) and in 16 pts (10.7%, BRAF V600E /other 9/7), respectively. Observed BRAF mutations other than BRAF V600E were located at kinase domain. The clinical outcomes of other BRAF mutations were worse similar to those of BRAF V600E and expanded RAS mutations (Table). Conclusions: Expanded BRAF mutations might predict a lack of response for mCRC pts who received anti-EGFR antibody. Further investigation is warranted to confirm the clinical impact of expanded BRAF mutations. [Table: see text]
Access to fertility preservation for cancer patients
Authors: J. Jacobs, L. Nohr Beck
Journal: Journal of Clinical Oncology (2008)

20610 Background: Sharing Hope is the only national fertility preservation financial assistance program for cancer patients. The cost of fertility preservation can be prohibitive due to timing, lack of insurance coverage, and cost of cancer treatments. The goal of Sharing Hope is to increase access to embryo/egg and sperm freezing. This evaluation will determine the geographic and financial impact of the program. Methods: Criteria for participation in Sharing Hope include: treatment plan presents risk of infertility as determined by an oncologist, medical determination by the patient’s oncologist and reproductive endocrinologist that treatments and associated medications are medically appropriate, and uninsured or denied insurance coverage for treatments and procedures. Participating centers provide reduced fee preservation services. In addition, EMD Serono, Inc. donates medications for one IVF cycle for women. Simple statistical analysis was used to determine geographic reach of the program and financial savings for participants. Results: From September 2004 through September 2007, 374 patients were approved. Between Year 1 and Year 3, the number of patients grew by 239%. Participants resided in 33 different states with the highest number from New York (19%), California (17%), and Texas (11%). The average savings per female was $3,019 for embryo freezing and $1,942 for egg freezing. Using wholesale acquisition cost of the fertility medications provided by EMD Serono, Inc., which may not be representative of actual purchase price, each approved female patient may have saved up to $3,778. The average savings per male was $452 for sperm freezing. Conclusions: The tremendous growth of Sharing Hope over the past 3 years demonstrates the high demand for financial assistance for fertility preservation. The approval of patients across the country shows the national impact of the program. As more oncology healthcare professionals refer patients to Sharing Hope and as more centers join Sharing Hope, the program will continue to grow. The total savings for the program was approximately $1,211,141. While the discounted costs of freezing are still relatively high, cost savings for patients compared to the full price are significant. Increased ability to access fertility preservation may increase survivors’ quality of life. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration EMD Serono, Inc. EMD Serono, Inc. EMD Serono, Inc.
Use and impact of bevacizumab in patients undergoing liver resection for metastatic colorectal cancer in routine clinical practice.
Authors: Edmond Michael Kwan, Belinda Lee, Hui-Li Wong, Margaret Lee, Rachel Wong, Jeremy David Shapiro, Matthew E. Burge, Lara Rachel Lipton, Suzanne Kosmider, Peter Gibbs
Journal: Journal of Clinical Oncology (2016)

698 Background: In metastatic colorectal cancer (mCRC) patients with isolated liver metastases, surgical resection offers the greatest likelihood of cure. Whilst for mCRC patients treated with palliative intent the addition of bevacizumab to the chemotherapy backbone is of proven benefit, whether to use bevacizumab in the resectable or potentially resectable population is a clinical dilemma. Methods: Consecutive patients who underwent resection of liver metastases were identified from a prospective Australian mCRC registry that captures comprehensive data on patient and tumor characteristics (including resectability), treatment and outcome. The use of bevacizumab in this setting was examined and the impact on outcomes was explored. Results: From a total mCRC population of 1,700 patients, 543 patients with liver-only mCRC were identified, of which 217 patients (40%) underwent liver resection. Perioperative chemotherapy was administered to 185 patients (85.3%), with bevacizumab added to chemotherapy in 73 (39.5%) patients. There was a trend for bevacizumab treated patients to be younger (median age 60.4 vs 65.1 years, p = 0.07) and fitter (mean Charlson score 2.22 vs 2.64, p = 0.054). Patients that received bevacizumab with perioperative chemotherapy were considerably less likely to have disease regarded as resectable at diagnosis (39 of 73 (53.4%) vs 95 of 112 (84.8%), p =&lt;.01). At 5 years, overall survival was similar for bevacizumab treated and non-treated patients (61.4% vs. 59.2%, HR 0.83, p=0.52). There were no deaths within 30 days of surgery in any patients. Conclusions: Despite limited evidence to support the use of bevacizumab in patients with resectable or potentially resectable liver-only mCRC, clinicians are not infrequently utilising this approach, particularly in younger and fitter patients and those not considered to have resectable disease at diagnosis. The addition of bevacizumab did not appear to impact survival outcomes. A multivariate analysis is underway to better define the impact of bevacizumab on survival outcomes.
The relationship between radiotherapy efficacy and statin (St) use in prostate cancer (PC): A retrospective study.
Authors: V. Rodriguez-Freixinos, L. Farinas-Madrid, R. Morales, G. Sánchez-Ollé, C. Suarez, J. Planas, C. Serrano, I. Giraldo, C. M. Valverde, J. Morote, X. Maldonado, J. Carles
Journal: Journal of Clinical Oncology (2011)

e15100 Background: Preclinical antiproliferative, proapoptotic, and radiosensitizing St properties have been previously described. In addition, St use has been associated with a lower risk of PC incidence, low prostate-specific antigen (PSA) at diagnosis and longer freedom from biochemical recurrence (FFBR). The aim of this study was to correlate pre-radiotherapy St use with the risk of biochemical relapse in PC patients (pts) treated with radical radiotherapy (RT) with concurrent androgen deprivation. Methods: Medical reports of 204 pts diagnosed with PC between 2000 and 2005 were reviewed, with a median follow-up of 54 months. Univariate and multivariate analysis were performed. Variables included were PSA at diagnosis, St treatment, clinical T stage (T1-2a vs T2b-c vs T3-4) and Gleason Score (GS). According to NCCN guidelines, risk category was defined as low (T1-T2a and PSA≤10 and GS ≤ 6), intermediate (T2b or 10<PSA<20 or GS=7) or high risk (≥T2c or PSA≤20 or GS 8-10). ASTRO criteria were used for biochemical progression. Results: Median (M) age was 71 y (range 47-84) and M radiation dose was 74 Gy. Twelve (6%), 41 pts (20%) and 149 pts (74%) were classified as low, medium and high risk respectively. Forty-six pts (23%) were taking St at diagnosis. No statistical differences were found between treatment groups regarding M age, risk category, clinical T stage, GS or M radiation dose. However, pts treated with St had a lower M PSA at diagnosis (7.95 vs 12.95) (p=0,197). At the time of analysis, only 32 pts (15.7%) had biochemical relapse (4 low risk, 6 intermediate, and 21 high risk). St use was not significantly associated with improved FFBR (p=0.641), regardless of risk group. In the multivariate analysis, none of the previous items was associated with FFBR. Conclusions: In our cohort, St use was not associated with a significant improvement in FFBR, in either risk group. Although there could be a bias due to the proportion of pts with high risk features with low rate of biochemical relapses. Our findings warrant further investigation.
Spanish customized adjuvant trial (SCAT) based on BRCA1 mRNA levels
Authors: M. Cobo, B. Massuti, T. Morán, I. Chaib, L. Pérez-Roca, U. Jiménez, D. Aguiar Bujanda, J. González-Larriba, J. Gómez, R. Rosell
Journal: Journal of Clinical Oncology (2008)

7533 Background: Patients (p) with low BRCA1 mRNA levels attained longer survival when treated with cisplatin-based chemotherapy (Taron et al. 2004), while p with high BRCA1 levels attained longer survival when treated with taxanes-based therapy (Quinn et al. 2007). Early NSCLC p whose tumors had high BRCA1 levels had significantly worse survival (Rosell et al. 2007). Upregulated BRCA1 is part of a characteristic gene signature in aggressive lung cancers (Deeb et al. 2007). Methods: Adjuvant chemotherapy was customized based on BRCA1 mRNA levels in 84/100 completely resected N1 and N2 NSCLC p. 11 p with high BRCA1 levels received docetaxel (doc); 29 p with intermediate BRCA1 levels received doc/cisplatin (cis); 44 p with low BRCA1 levels received cis/gemcitabine (gem). Results: Median survival has not been reached in p with high or intermediate BRCA1 levels, while it is 25.6 months (m) in p with low levels (P=0.04). In a multivariate analysis for survival in all 84 p, the hazard ratios (HR) were 5.23 for p with high BRCA1 levels (P=0.07), 3.57 for p with tumor size > 4 cm (P=0.07). In the multivariate analysis of 42 N2 p, the HRs were 0.13 for 18 p receiving postoperative radiotherapy (P=0.04) and 22 for 15 p with intermediate or high BRCA1 levels (P=0.01). Conclusions: Interim analyses show that single-agent doc has no detrimental effect on survival in comparison with doc/cis. In addition, high BRCA1 mRNA expression could be a poor prognostic marker. The Spanish Lung Cancer Group has opened a phase III study of customized adjuvant chemotherapy based on BRCA1 mRNA levels. N2 p HR (95% CI) p Post-operative radiotherapy Yes 18 0.12 (0.02–0.89) 0.04 No 24 1 BRCA1 mRNA levels Low 24 1 Intermediate/High 15 22.43 (2.02–248.62) 0.01 Tumor size ≤ 4 24 1 > 4 18 1.63 (0.34- 7.91) 0.54 No significant financial relationships to disclose.