tbuckley/cabot-search huggingface dataset:
Standard chemotherapy strategy versus changing chemotherapy strategy as to FDG-PET response after first cycle of standard chemotherapy for advanced NSCLC.
Authors: S. Kim, J. E. Kim, K. Kim, D. H. Lee, C. Choi, D. H. Moon, J. Ryu, S. J. Oh, C. Suh, J. Lee
Journal: Journal of Clinical Oncology (2011)

7558 Background: Reduction of metabolic activity after one cycle of chemotherapy is closely correlated with clinical outcome in non-small cell lung cancer patients. The aim of this study was to evaluate whether changing chemotherapy according to response of positron emission tomography (PET) after 1st cycle of chemotherapy improve overall response rate (ORR). Methods: This is an open-label, 2-arm, randomized, prospective study of 100 patients. While arm A received 4 cycles of GPMP (GenexolPM 230 mg/m2 and cisplatin 60 mg/m2 on Day 1, every 3 weeks) based on conventional radiologic assessments every 6 weeks, arm B changed chemotherapy regimen to 4 cycles of GemOx (gemcitabine 1000 mg/m2 on Day 1 and 8 and oxaliplatin 130 mg/m2 Day 8, every 3 weeks) when PET failed to show metabolic response (reduction of tumor FDG uptake more than 20%) after 1st cycle of GPMP. ORR, progression free survival (PFS), and overall survival (OS) were compared. Results: Of 100 patients, 49 patients were randomized to arm A and 51 patients to arm B. Age, gender, performance status and smoking history were not different between groups. ORR was 26.8% in arm A and 47.1% in arm B, but there was no statistical difference (p=0.090). PFS (arm A, 4.6 months vs. arm B, 4.9 months) and OS (18.2 vs. 14.2 months) were not significantly different (p=0.354 and p=0.282, respectively). There were no difference in incidence of grade 3 or 4 hematologic (arm A, 12.8% vs. arm B, 18.8%; p=0.575) and non-hematologic toxicities (26.5% vs. 20.4%; p=0.631). Six patients in arm A and 2 patients in arm B discontinued treatment due to adverse events. PET after 1st cycle was performed in 36 (73.5%) patients of arm A. Sensitivity and specificity for prediction of best response was 81.8% (95% confidence interval [CI], 52.3–94.9%) and 47.1% (95% CI, 26.2–69.0%), respectively. Conclusions: Although PET-guided chemotherapy regimen changes after first cycle of chemotherapy improved ORR, it lacked statistical significance. In addition, PFS and OS were not improved. The high sensitivity (81.8%) of PET for prediction of best response suggests that reduction of metabolic activity observed in PET is closely correlated with final outcome of therapy.
Generation of virtual control groups for single-arm prostate cancer (PCa) adjuvant trials.
Authors: Zhenyu Jia, Michael B. Lilly, James A. Koziol, Herbert Ruckle, Christine E. McLaren, Thomas Ahlering, Douglas Skarecky, Dan Mercola
Journal: Journal of Clinical Oncology (2013)

239 Background: It is difficult to construct a control group for trials of adjuvant Rx of PCa after radical prostatectomy (RP) due to ethical issues, patient acceptance. We present an algorithm involving 8 regression models to generate virtual control groups based on the Kattan post-prostatectomy nomogram. Methods: The online Kattan nomogram gives the probability of being progression-free at 2, 5, or 7yr after RP without adjuvant Rx. For each subject we estimate the progression-free survival (PFS) from these data by applying 8 models that use curve fitting and estimation of time to relapse. The models estimated time to 60%, 65%, . . . 95% chance of relapse for each subject. To prepare a virtual control group for a single-arm adjuvant Rx trial, the predicted PFSs generated from the optimum model are compared with the observed PFSs by the logrank test. Results: The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx. The optimum model depended on the clinical features of the test population. Higher relapse risk required a higher stringency model. The algorithm was validated with an independent dataset of 155 post-RP patients. When analyzed by the optimum model there was high correlation between the group observed, predicted PFSs (p = 0.792 for no difference). We created a virtual control group for pts on a Ph II trial of adjuvant chemohormonal Rx post RP. The observed PFSs for these subjects were significantly longer than the PFSs predicted by the new algorithm, indicating that the adjuvant Rx is highly effective in prolonging PFS after RP in pts at high risk for PCa recurrence. This was confirmed by comparing observed PFSs with PFSs of a matched historical group. Conclusions: The algorithm can accurately generate control groups for single arm adjuvant Rx trials for PCa, facilitating development of new therapeutic strategies.
Use of soluble isoforms of vascular endothelial growth factor to predict response to sunitinib in metastatic renal cell carcinomas.
Authors: B. Paule, L. Bastien, E. Deslandes, B. Naimi, O. Cussenot, A. de la Taille, F. M. Calvo, S. Mourah
Journal: Journal of Clinical Oncology (2010)

e13508 Background: Angiogenesis is the target of several agents in the treatment of malignancies, including renal cell carcinoma (RCC). There is a real need for surrogate biomarkers that can predict selection of patients who may benefit from antiangiogenic therapies, prediction of disease outcome and which may improve the knowledge regarding mechanism of action of these treatments. Tyrosine kinase inhibitors (TKI) have proven efficacy in metastatic RCC (mRCC). However, the molecular mechanisms underlying the clinical response to these drugs remain unclear. The present study aimed to identify molecular biomarkers associated with the response to sunitinib, a TKI. Methods: To evaluate this relationship, primary tumors from 23 clear-cell metastatic RCC patients treated by sunitinib were analyzed for a panel of 16 biomarkers involved in tumor pathways targeted by sunitinib, using real-time quantitative reverse- transcriptase PCR. Results: Eighteen of the 23 patients (78%) responded to sunitinib (9 responses and 9 stabilizations). Among transcripts analyzed, only the levels of vascular endothelial growth factor (VEGF) soluble isoforms (VEGF121 and VEGF165) were associated with the response to sunitinib. Indeed, the tumor transcript levels were significantly higher in responding patients compared with patients who had a failure to treatment: median 1222 versus 241 for VEGF121 (p = 0.04), and median 905 versus 352 for VEGF165 (p = 0.04). For tumors overexpressing VEGF121 and VEGF165, the probability of response was 81% and 90%, respectively. Furthermore, the ratio of VEGF soluble isoforms (VEGF121/VEGF165) was significantly associated with prognosis. Indeed, the overall survival of patients with a ratio lower than 1.25 (cut-off value determined from the third quartile) was significantly higher than those of patients with a ratio higher than 1.25 (p = 0.02; median survival time not reached, versus 25.2 months). Conclusions: This preliminary study provides a promising tool that might help in the management of metastatic RCC, and could be extended to other tumors treated by TKI. No significant financial relationships to disclose.
Efficacy and tolerability of bevacizumab (BEV) plus capecitabine and cisplatin (XP) in Chinese patients (pts) with locally advanced or metastatic gastric/gastroesophageal junction cancer (AGC): Results from the AVATAR study.
Authors: Lin Shen, Jin Li, Jian-Ming Xu, Hong-Ming Pan, Guanghai Dai, Shukui Qin, Liwei Wang, Jinwan Wang, Zhenzhou Yang, Shu Yongqian
Journal: Journal of Clinical Oncology (2012)

73 Background: In the AVAGAST study, chemotherapy (fluoropyrimidine and cisplatin) + BEV did not significantly improve overall survival (OS) vs. chemotherapy + placebo. Geographic differences in efficacy were observed, but only 12 Chinese pts were included. AVATAR, a study similar in design to AVAGAST, is a randomized double-blind study conducted exclusively in China in pts with AGC. Methods: Pts aged &gt;18 years with gastric adenocarcinoma were randomized 1:1 to XP + BEV 7.5 mg/kg or placebo + XP. The primary objective was OS; secondary objectives included progression-free survival (PFS) and safety. Results: Baseline characteristics of the 202 pts were well balanced. The primary efficacy endpoint of improved OS in the BEV arm was not met (HR 1.11, 95% CI 0.79–1.56; p=0.5567; see table ). BEV + XP was well tolerated. Grade 3–5 adverse events (AEs) and serious AEs were 60% and 19% for BEV and 68% vs. 21% for placebo, respectively. Grade 3–5 AEs of special interest with BEV occurred in 8% of BEV pts and 15% of placebo pts; the difference was mainly due to grade 3–5 haemorrhage (BEV 4%, placebo 12%). Conclusions: Addition of BEV to XP in Chinese pts with AGC did not significantly improve outcomes in AVATAR. The results from AVATAR are consistent with the findings seen in the Asian sub-population of the previous AVAGAST study. [Table: see text]
Does receptor status impact survival of patients with mid-gut neuroendocrine tumors?
Authors: Yi-Zarn Wang, David T Beyer
Journal: Journal of Clinical Oncology (2016)

227 Background: Neuroendocrine tumors (NETs) are rare neoplasms increasing in incidence due to greater awareness among patients and physicians. The most reliable diagnostic imaging study has been the 111 In-pentetreotide scan which binds to somatostatin receptors of the tumor. It is known that breast cancer treatment outcome is tightly correlated with degree of tumor cell differentiation and receptor status. We hypothesize that receptor status determined by 111 In-pentetreotide (Octreoscan) and 123 I-Metaiodobenzylguanidine (MIBG) imaging results can predict prognosis for small bowel NETs. Methods: A database with all patients seen at the LSU/Ochsner NET Program was queried for nuclear medicine scan results. Included patients had a histologically confirmed ileal, jejunal, or small intestinal NET and Octreoscan and MIBG imaging results. Kaplan-Meier survival analysis was performed and statistical significance was determined by Log-rank test (p&lt;0.05). Results: 110 patients diagnosed between July 1994 and September 2013 were included. There were 64 females (64/110, 58%) and 46 males (46/110, 42%). Seventy-three (73/110, 66%) and sixty-three (63/100, 57%) patients had positive Octreoscan and MIBG imaging results, respectively. 5- and 10-year survival was calculated and sorted into four groups based on imaging positivity. Conclusions: Most midgut NETs present with positive Octreoscans which reflect positive receptor status; a favorable feature in prognosis based on the well-established breast cancer treatment experience. Unexpectedly, our data have shown receptor scintigraphy studies result has no baring in short term survival. More surprisingly, patients with double positive scan demonstrate a substantial survival disadvantage over a longer interval. Further longitudinal studies are required to determine if NET receptor status can reliably predict patient prognosis and the mystery of the reversal relation of the receptor status of NET patients and their prognosis. [Table: see text]
Effect of Adding Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy Consolidation to Three Cycles of CHOP Plus Involved-Field Radiotherapy for Limited-Stage Aggressive Diffuse B-Cell Lymphoma (SWOG 0313)
Authors: Thomas P. Miller, Joseph M Unger, Catherine Spier, Baldassarre Stea, Oliver W. Press, Jonathan W. Friedberg, Michael LeBlanc, Richard I Fisher
Journal: Blood (2008)
Different outcomes of cardiologic safety of trastuzumab in adjuvant or metastatic setting in patients with breast cancer: A single institution experience.
Authors: G. Scandurra, R. A. Aiello, E. Taibi, M. V. Sanò, M. Ali, G. Fallica, M. Chiarenza, A. Mazzola, R. Di Marco, S. Clementi, M. G. V. Di Leo, E. Miano, M. Caruso
Journal: Journal of Clinical Oncology (2011)

e11028 Background: Trastuzumab is a monoclonal antibody developed to target HER 2 receptor inhibit tumour cells proliferation that overexpress HER 2.Trastuzumab is active and is viable in breast cancer in neoadjuvant, adjuvant or metastatic setting. The most serious adverse event of trastuzumab is cardiotoxicity. We evaluate different cardiologic toxicity in patients with breast cancer treated with trastuzumab in metastatic or adiuvant setting. Methods: Jan 2006 - Dec 2010 were treated, 84 patients with metastatic breast cancer (MBC). While Aug 2006 - Dec 2010 were admitted 140 patients affected by breast cancer treated in adjuvant setting of whom 110 able to be assessed. MBC sample: 84 patients (2M/82 F) median age 54 (range 27-86 yy). 77 patients underwent surgery for primary tumor. 70 have received also complementary radiotherapy and 62 patients have received adjuvant chemotherapy with antracyclines and 14 chemotherapy without antracyclines. In the metastatic setting patients have started trastuzumab following - in median of 37 months (range 6-192 months) - adjuvant chemotherapy and were treated for 23 months (range 3-49 months) in concomitant regimen with taxanes, vinorelbine or platinum-derived in 3 median lines (1-10 lines). In adjuvant setting sample (n = 110), the median age was 53 years (range 23-83 yy). The whole group underwent surgery and received adjuvant anthracyclines, 47 also taxanes, 89 adjuvant radiotherapy, followed by one year of trastuzumab after a time of 1-3 months. Cardiotoxicity has been assessed every 3 months, by Echocardiography and % LVEF. Results: 6 pts affected by MBC (7,1%) had hearth failure, class III of NYHA, 3 patients have discontinued trastuzumab treatment for 2 months. In adjuvant setting severe cardiotoxicity leading to stop therapy was recorded in 8 patients (7,2%), class III of NYHA, while 13 patients have discontinued treatment for LVEF droop for 1or 2 month. Conclusions: Trastuzumab in general has an acceptable cardiologic toxicity. However, we’ve noticed that cardiologic safety is lower in adjuvant setting than in MBC, probably because - in adjuvant administration - antracyclines and other adjuvant therapy are closer.
TFAP2E methylation status in patients with metastatic colorectal cancer treated with FOLFIRI.
Authors: Seong Joon Park, Seung-mi Kim, Yong Sang Hong, Jae-Lyun Lee, Jeong-Eun Kim, Kyu-Pyo Kim, Dong-Hoon Jin, Tae Won Kim
Journal: Journal of Clinical Oncology (2014)

515 Background: Transcription factor AP-2ε, a member of the AP-2 family has been extensively studied in many cancers. Recently, it has been suggested that the gene encoding AP-2ε (TFAP2E) is involved in the development of colorectal cancer (CRC) and is also associated with clinical non-responsiveness to chemotherapy in CRCs. Therefore, we have investigated the clinical significance of TFAP2E methylation status in patients with metastatic CRCs who have received combination chemotherapy with fluoropyrimidine, leucovorin, and irinotecan (FOLFIRI) as first-line treatment. Methods: Eligible patients were those with metastatic CRC treated at Asan Medical center from Jan 2009 to June 2012, and treated with first-line FOLFIRI chemotherapy. The patients without available surgical tissue were excluded. A total of 94 patients were finally included in the study. Results: Forty patients (43%) showed TFAP2E hypermethylation (HM group), and 54 patients (57%) showed TFAP2E hypomethylation (LM group). There were no statistically significant differences in the baseline characteristics according to TFAF2E methylation status. Response rate to chemotherapy was not significantly different between 2 groups (response rate, 50% in HM vs. 36% in LM group, p=0.200; disease control rate, 87% in HM vs. 85% in LM group, p=0.819). After a median follow-up duration of 39.9 months, both progression-free survival (PFS) and overall survival (OS) were not significantly different between 2 groups (HM group vs. LM group; PFS, 5.93 months vs. 5.90 months, p=0.893; OS, 20.9 months vs. 19.8 months, p=0.966). Multivariate analysis showed that there was no significant factor associated with PFS. The patients with well or moderately differentiated tumors showed better OS compared to those with poorly differentiated or mucinous tumors (hazard ratio 0.27, 95% confidence interval 0.13-0.55, p&lt;0.001). However, TFAP2E methylation status was not an independent factor affecting neither PFS nor OS. Conclusions: TFAP2E methylation status may not be a useful biomarker in predicting the clinical outcomes in patients with metastatic colorectal cancers who have received first-line FOLFIRI chemotherapy.
Prognostic relevance of B7H1 and B7H3 protein expressions in metastatic clear cell renal cell carcinoma.
Authors: J. Mischinger, E. Froehlich, A. Griesbacher, K. Pummer, S. Mannweiler, R. Zigeuner, K. Lipsky
Journal: Journal of Clinical Oncology (2010)

e15074 Background: The aim of the study was evaluate B7-H1 and B7-H3 glycoprotein expressions in tumor tissue of patients with clear cell renal cell carcinoma (CC-RCC). Methods: 78 patients affected by metastatic CC-RCC and undergoing interferon treatment between 1996 and 2005 were included in the study. The tumor tissue on the histopathologic slides was re-evaluated for clear cell origin by a pathologist who regarding primary diagnosis and patients' outcome. Finally, 45/78 patients were eligible. Nephrectomy specimens were immunostained using antibodies targeting B7-H1 and B7-H3 glycoproteins. The stained tumor tissue was scanned and digitized. The regions of positive staining were processed with the Image Scope software and expressed as a certain percentage rate of the predefined tumor-tissue. The percentage of glycoprotein-expression was associated with overall survival using the Kaplan-Meier method and the log rank test. Pathologic parameters of the SSIGN-score defined by the Mayo Clinic were compared with protein expression and survival. Results: There was no significant association between B7-H1 expression and survival or SSIGN-score. In contrast, B7-H3 expression was significantly associated with survival at a cutoff-level of 15% immunoreactivity. Furthermore we found that patients with a SSIGN-score 0-4 showed a 4% lower B7-H3 expression than those with a score 5-13. The multivariate model which included both, glycoproteins and SSIGN-score showed that patients with a SSIGN-score of 4-6, and 0-3, respectively had no survival advantage anymore after 50, 150 months of survival compared to a SSIGN-score of 7-9. Conclusions: In our study the B7-H1 glycoprotein could not be demonstrated as a prognostic factor. In contrast the B7-H3 glycoprotein could be proven as prognostic factor whose amount of expression correlates with survival and malignity (SSIGN-Score) of the CC-RCC. On the other hand according to our results, the SSIGN-Score seems to be a prognostic marker, which loses influence as it comes to advanced survival. In future B7-H3 could be used as an important prognostic factor for adjuvant and targeted therapy methods. No significant financial relationships to disclose.
Prospective phase I/II trial of dose-painting prostate brachytherapy guided by cancer-specific ultrasound-based tissue-type imaging (TTI).
Authors: Ronald D. Ennis, Frieda Trichter, Kunal Saigal, Stuart A. Quinn, Ernest J. Feleppa
Journal: Journal of Clinical Oncology (2014)

246 Background: Standard treatments treat the entire prostate gland uniformly, while focal treatments target only the dominant tumor. We propose an alternative approach wherein tumor areas are treated with an escalated dose of radiation while the remainder of the prostate with dose de-escalation. Tissue-type images (TTIs), which identify intraprostatic tumors via ultrasound spectral analysis, were used to identify tumors. Methods: 14 low risk patients were enrolled. TTIs and standard B-mode ultrasound images were generated and fused intraoperatively. Based on TTIs, plans were developed to deliver 200% prescription dose to the tumors and 100% to the prostate. Doses above 100% to non-tumor regions were minimized and standard normal tissue constraints were respected. Results: 12 patients were successfully treated. Technical problems occurred in the first patient and another received a standard implant due to discordance of TTIs with MRI and biopsy findings. One patient passed away soon after the procedure of unrelated cause. A total of 28 tumors were identified in these 12 patients (median 2 tumors/patient, range 1-4). Mean tumor volume was 0.72cc (range 0.03cc -4.07cc). Tumor dose was significantly higher in TTI-based plans, with mean tumor V200%: TTI vs. standard 97% vs. 48%, p&lt;0.05. Modest dose reduction of the whole prostate was also achieved. Median follow-up was 25.7 months (range 21.3-48 months). A low incidence of grade 2 toxicities and no grade 3-4 toxicities were seen (Table). Two patients experienced a biochemical failure per the nadir+2 definition, both failures are attributable to PSA bounce (PSA down to 1.0 and 0.59 at 42 and 30 mos., respectively). Post-treatment biopsies have been performed on 5/11 patients (4 refused), with 2 patients with pending biopsies. 4/5 available biopsies are negative, with 1 patient having a small focus of residual cancer. Conclusions: Dose-painting prostate brachytherapy is technically feasible. This tumor-directed approach, more rational than uniform whole gland treatments, offers the promise of excellent cancer control, low toxicity and low risk of re-treatment. Clinical trial information: NCT01227642. [Table: see text]
Differential expression of FOXF1 in bladder cancer metastases and association with established bladder cancer subtypes.
Authors: Debasish Sundi, Woonyoung Choi, Isuru Sampath Jayaratna, David James McConkey, Colin P. N. Dinney
Journal: Journal of Clinical Oncology (2016)

464 Background: FOXF1 is a transcription factor that may act as a tumor suppressor by interaction with p53. We identified FOXF1 to be highly differentially expressed in a discovery set of primary bladder cancers and matched nodal metastases. Here we study FOXF1 in preclinical models and define the association of FOXF1 with clinical bladder cancer phenotypes in several independent cohorts. Methods: Whole genome mRNA gene expression profiling (GEP) using Illumina HT12v3-4 chips was performed on paired primary tumors and nodal metastases from a cystectomy cohort. Among the top differentially expressed genes, FOXF1 was identified as a candidate regulator of cancer cell invasion. Murine orthotopic xenografts were established from human bladder cancer cell lines (UC-3, UC-14), and mRNA expression was assessed by real-time PCR. Four independent clinical cohorts with GEP data were subtyped as luminal, p53-like, or basal according to a validated gene expression signature (Choi et al., Cancer Cell2014). Associations between FOXF1 expression with survival after cystectomy (adjusted Cox models) and bladder cancer subtype (ANOVA) were assessed. High gene expression was defined as expression &gt; median. Results: In the initial discovery set, FOXF1 expression was 3.6-fold lower in nodal metastases than paired primary tumors (n = 33, p &lt; 0.001). Among xenografts with nodal metastases, FOXF1 expression was 1.4-fold lower in the metastases (n = 9, p = 0.0886). In two clinical cohorts (MDA Discovery n = 73 and GSE13507 n = 55), high FOXF1 expression was associated with improved cancer specific survival (HR = 0.35, p = 0.046) and overall survival (HR = 0.45, p = 0.006), respectively. In two other cohorts (MDA Validation n = 57 and GSE32894 n = 93), FOXF1 was not associated with survival after treatment. In all four cohorts, FOXF1 was most highly expressed in tumors subtyped as p53-like (p ≤ 0.0024 for all cohorts). Conclusions: FOXF1 is differentially expressed between primary and metastatic bladder cancer lesions. Across multiple independent cohorts, FOXF1 is more highly expressed among p53-like tumors known to be resistant to neoadjuvant chemotherapy, suggesting that this may be a novel predictive biomarker.