tbuckley/cabot-search huggingface dataset:
Pemetrexed and cisplatin with concurrent thoracic radiation therapy (TRT) followed by docetaxel in stage III non-small cell lung cancer (NSCLC) patients (pts)
Authors: S. M. Gadgeel, J. C. Ruckdeschel, A. Wozniak, B. Patel, L. K. Heilbrun, W. Chen, R. Venkat, R. Chaplen, A. Turrisi
Journal: Journal of Clinical Oncology (2008)

7569 Background: Standard treatment of stage III NSCLC remains concurrent chemotherapy and TRT. However, not all chemotherapy drugs can be combined with TRT at full systemic dosages. We are conducting a phase II study evaluating the combination of pemetrexed and cisplatin, at full systemic doses with TRT followed by docetaxel in stage III NSCLC pts. Methods: Eligibility includes stage IIIA or IIIB NSCLC, PS ≤ 1, FEV1 ≥ 1 liter, diffusion capacity ≥ 50%, predicted V20 ≤ 40%. Pts were treated with pemetrexed at 500 mg/m2 and cisplatin every 3 weeks for 3 cycles with concurrent TRT to 66 Gy. First 6 pts received cisplatin at 60mg/m2 and the following 11 pts received cisplatin at 75mg/m2. After concurrent therapy, pts received docetaxel at 75mg/m2 every 3 weeks for 3 cycles with growth factor support. Planned accrual is 28 pts. Results: 17 pts have completed therapy. Pt. characteristics: median age- 58 years(47–77), 59% males, 65% stage IIIB, 59% adenocarcinomas. Median FEV1 was 2.3 liters (1.1–3.4) and median predicted V20 was 30% (7–40). 12 pts (71%) have completed all 6 cycles of chemotherapy without dose reduction and received TRT to 66 Gy. Three more pts received all 3 cycles of cisplatin and pemetrexed with TRT. Grade 3–4 toxicities, all observed during concurrent therapy, were grade 3 neutropenia- 6 pts, grade 4- thrombocytopenia- 1 pt, grade 3 renal failure- 2 pts, grade 3 pneumonitis- 1 pt. No grade 3–4 esophagitis was observed. Three pts were hospitalized for treatment related toxicities during the concurrent treatment. Confirmed response by RECIST criteria was observed in 9 pts (53%, Wilsons 90% CI- 34%-71%). 4 other pts had tumor shrinkage. 4 pts have progressed- 2 pts had brain as the only site of progression. Conclusions: The combination of pemetrexed and cisplatin at full systemic doses with concurrent TRT followed by docetaxel is feasible in pts with stage III NSCLC. Toxicity and efficacy with this regimen, in treated pts, compare favorably with other regimens tested. Accrual to the study is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly
A phase II trial of panitumumab with irinotecan and S-1 (IRIS) as second-line treatment in patients with wild-type <i>KRAS</i> metastatic colorectal cancer.
Authors: Rai Shimoyama, Tetsuo Kimura, Toshi Takaoka, Kazuki Sakamoto, Shunji Kawamoto, Koji Yoshizaki, Yuji Negoro, Fuminori Goda, Akihito Tsuji, Tsuyoshi Nakayama, Hiroshi Miyamoto, Tetsuji Takayama, Yoshiro Niitsu
Journal: Journal of Clinical Oncology (2015)

732 Background: Panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in second-line chemotherapy increased objective response rate and prolonged progression-free survival (PFS) versus FOLFIRI alone in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) (Peeters et al, J Clin Oncol 2010). This trial (UMIN000004659) evaluated tolerability and efficacy of combination therapy with irinotecan and S-1, an oral fluoropyrimidine (IRIS) plus panitumumab as second-line chemotherapy in patients with WT KRASmCRC. Methods: Main inclusion criteria were: patients with WT KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/m 2 ) and irinotecan (100 mg/m 2 ) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was completion rate of protocol therapy (CRT). The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: Thirty-seven patients were enrolled in 9 centers. The overall CRT was 62.2% (23/37). Most frequent grade 3/4 toxicities were: skin rash (24%), diarrhea (16%), and appetite loss (11%). The overall RR was 32.4% (12/37). Of these, four patients underwent conversion surgery. Median PFS and OS were 9.5 months (95% CI: 3.5-15.4 months) and 20.1 months (95% CI: 16.7-23.2 months), respectively. Conclusions: IRIS plus panitumumab has acceptable toxicity profile and promising efficacy in patients with previously treated WT KRAS mCRC. This regimen can be an additional treatment option for second-line chemotherapy in WT KRAS mCRC. Clinical trial information: UMIN000004659.
Surgery in pancreatic cancer (PC): Identifying potential barriers.
Authors: M. S. Beg, O. O. Olowokure, M. Atiq, S. A. Ahmad
Journal: Journal of Clinical Oncology (2011)

290 Background: Due to lack of effective systemic therapy, surgical resection remains the mainstay of treatment of PC and the only potential for cure. Even though mortality of PC surgery has decreased in recent years, surgical rates remain lower than for other cancer types. We performed an analysis of early-stage PC to determine factors that may prevent patients from undergoing surgery. Methods: PC cases diagnosed between 1996 and 2008 were identified from the Veteran's Affairs Central Cancer Registry. Patients with early stage disease, defined as AJCC clinical stage group 1-3, were included. Data were analyzed using biostatistical software SPSS. Chi-square analysis was performed for categorical variables comparing those who underwent surgery (SUR) and those in which surgery was not performed (SNP). Kaplan-Meier analysis was used for estimates of overall survival. Results: Of 1,306 cases identified, 97.7% were male, 78% where white. Surgery was performed in 251 (19.2%) cases. Surgery was not recommended in 739 (56.6%) and contraindicated due to patient related factors in 198 (15.2%) cases. Surgery was recommended but not performed due to unknown reasons in 59 (4.5%); patient refusal in 43 (3.3%) and “other reasons” in 16 (1.2%) cases. Mean age in SUR vs. SNP was 64.1 vs. 67.5 years. Median survival was 11.1 months in SUR vs. 5.5 months SNP (p&lt;0.001). On univariate analysis, patients with diabetes had less surgery (10.5%) compared to other comorbidities (p&lt;0.001). Tumors in the body of the pancreas had less surgery (4.8%) compared to the head or tail (19.9%, 23.6%, p&lt;0.001). Sex, race, alcohol, and tobacco use did not significantly impact surgery rates (p&gt;0.05). On multivariable analysis including race, sex, primary site, comorbidity, chemotherapy, radiation, alcohol, and tobacco use, only comorbidity was independently associated with less surgery. Conclusions: In this registry-based, retrospective analysis of early stage PC, although SUR patients had better survival than SNP, surgery was not recommended as a treatment option for most patients by their providers. Whereas comorbid conditions do seem to influence this decision, race and patient refusal was not a major factor. No significant financial relationships to disclose.
Yoga program for patients with brain tumors undergoing radiotherapy (XRT) and their family caregivers.
Authors: Kathrin Milbury, Smith Mallaiah, Anita Mahajan, Terri S. Armstrong, Shiao-Pei S. Weathers, Kathryn E Moss, Nazli Goktepe, Amy Spelman, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2016)

200 Background: The role of behavioral medicine in the symptom management of glioma patients is largely unknown. Moreover, although the literature revealed that family caregivers are at risk of physical and psychological burden, the needs of caregivers generally remain unaddressed. The purpose of this study was to establish feasibility and preliminary efficacy of a couple-based Yoga (CBY) intervention in glioma patients and their caregivers targeting QOL outcomes. Methods: This small, single-arm pilot trial included adults with low and high grade glioma undergoing XRT and their family caregivers. Dyads participated in a 12-session CBY program focusing on breathing exercises, gentle movements and guided meditations. We tracked feasibility data and assessed levels of cancer-related symptoms (MDASI), depressive symptoms (CES-D), fatigue (BFI), sleep disturbances (PSQI), spiritual well-being (FACT-SP) and overall mental and physical QOL (SF-36) at baseline and post-CBY, which was at the end of XRT. Participants also completed program evaluations. Results: We approached 7 dyads of which 5 (71%) consented. All participants completed all 12 sessions and pre/post assessments. All patients (mean age: 52 yrs., 80% female, 80% high grade) and caregivers (mean age: 58 yrs., 60% female, 60% spouses) indicated that they perceived benefit from the program. Paired t-tests revealed a marginally significant, yet clinically meaningful, decrease in patient’s cancer symptoms (t = 2.32, p = .08; MDASI mean; 32.06 vs.18.80). There were clinically significant reductions in patient sleep disturbances (PSQI mean: 10.75 vs. 8.00) and improvements in patient and caregiver mental QOL (MCS of SF-36 mean: 42.35 vs 52.34 and 45.14 vs 51.43, respectively). All other means were generally in the expected direction. Conclusions: This novel supportive care program appears to be safe, feasible, acceptable, and subjectively useful for glioma patients and their caregivers. Although the trial did not have a control group, it is notable that multiple symptom outcomes improved when they would normally have been expected to deteriorate over the course of XRT. We are currently conducting a randomized controlled trial to examine treatment efficacy. Clinical trial information: 2015-01124.
Initial evaluation of patients diagnosed with pancreatic cancer within a community health system.
Authors: Kathryn Tzung-Kai Chen
Journal: Journal of Clinical Oncology (2015)

269 Background: The management of pancreatic patients who are referred to a tertiary care center is well described. However, many patients receive their initial evaluation and care at community health systems. We sought to describe how patients present within the community, the patterns of initial evaluation, and the impact on management. Methods: In a period spanning 3 years (2010-2013), 82 patients were newly diagnosed with pancreatic cancer, as identified by a cancer registry at a community health system. Under IRB approval, data regarding patient characteristics, initial evaluation, and management were retrospectively collected from the electronic medical record (EMR) and analyzed. Results: Of the 82 patients, 68 patients had sufficient data available in the EMR for analysis. Thirty-two patients (47%) initially presented to outpatient clinic, and 36 patients (53%) presented to the emergency department. The presenting complaint was identified as abdominal pain in 33 patients (49%), jaundice in 20 patients (29%), and general malaise in 9 patients (13%). Patients who presented through outpatient clinic vs. emergency department received similar initial imaging studies upfront, including CT of the abdomen and pelvis (61% vs. 72%) and abdominal ultrasound (27% vs. 17%). Sixteen percent of those patients evaluated in outpatient clinic were subsequently admitted, compared to 94% of those patients evaluated in the emergency department. Finally, 31% of those presenting in outpatient clinic eventually underwent surgical resection, compared to 8% of those presenting through the ER, and the median time to surgery for the entire cohort was 1.1 months. Conclusions: Within the community, half of all patients present through the emergency department, and the majority of these are admitted for work up and management of symptoms. In contrast, those patients who present through outpatient clinic are less likely to be admitted, and are more likely to undergo definitive resection. This likely represents a disparity on several levels: the acuity of patients presenting to the emergency department vs. clinic, and how they are managed in each setting.
Multicenter phase I trial of sorafenib (S) in high-risk hepatocellular carcinoma (HCC) patients after liver transplantation (LT).
Authors: Abby B. Siegel, Anthony B. El-Khoueiry, Richard S. Finn, Abhishek Goyal, Charles David Blanke, Robert S. Brown
Journal: Journal of Clinical Oncology (2014)

285 Background: LT offers excellent long-term survival for HCC patients within the Milan criteria. For those outside Milan, recurrence rates are higher. No known treatments have been shown to decrease risk of recurrence post-transplant. Methods: Subjects had pathologically proven HCC that was outside Milan (pre- or post-transplant), was poorly differentiated, or had vascular invasion. We used a standard 3+3 design, beginning drug between 4 and 16 weeks after LT, with planned duration of treatment of 24 weeks. Cohort dosages were: 1) 200 mg q day, 2) 200 mg BID, 3) 200 mg/400 mg q day. Correlative studies included circulating endothelial cells (CECs-Veridex) and plasma biomarkers (VEGF, sVEGFR1, sVEGFR2, IL-6 and HGF) collected prior to treatment, at 1 month, and at recurrence. Results: We enrolled 14 patients; 93% were men. Median age was 63; 71% had underlying HCV, 21% HBV, and 21% ETOH. 57% were outside Milan on preoperative imaging. On explant, 29% had poorly-differentiated tumors, and 36% had vascular invasion. MTD was 200 mg BID; only 43% of patients received &gt;80% of planned dose. DLTs included liver function abnormalities (1), transplant rejection leading to death (1), and grade 3 hypertension (1). Grade 3-4 toxicities seen in &gt;10% of subjects included: leukopenia (29%), LFT abnormalities (21%), hypertension (14%), hand-foot syndrome (14%) and diarrhea (14%). Over a median follow-up of 836 days, 1 patient died and 4 recurred (median time to recurrence=716 days). Two recurrences were in subjects with limited exposure to S. Median CEC number at baseline was 16 cells/4 ml for those who recurred, and 42 cells/4 ml for those who did not (p=0.10). Median sVEGFR2 levels decreased after 1 month on S (p=0.09), but did not predict recurrence. Conclusions: To our knowledge, this is the first multicenter phase I trial of S completed in the post-transplant setting for high-risk HCC. MTD of S was 200 mg PO BID. Post-transplant S was feasible. Exploratory biomarker data suggest that low CECs at baseline were potentially associated with a higher recurrence rate. Time to recurrence was promising compared with historic controls, but needs to be further explored and validated in a larger study. Clinical trial information: NCT00997022.
Association of reduced <i>GATA1</i> mRNA expression with clinicopathology and shortened recurrence-free survival in clear cell renal cell carcinoma.
Authors: Inga Peters, Natalia Dubrowinskaja, Michael Kogosov, Mahmoud Abbas, Joerg Hennenlotter, Mario W. Kramer, Ralph Scherer, Axel S. Merseburger, Markus A. Kuczyk, Juergen Serth
Journal: Journal of Clinical Oncology (2014)

521 Background: GATA1, a zinc-finger transcription factor and member of the GATA family proteins 1-6, is known to be involved in cell growth and apoptosis, especially in the erythroid lineage. Recent studies demonstrated that GATA1 interacts with p53 and its overexpression leads to an inhibition of the p53 gene function. Increased p53 expression levels have been shown to be associated with prognosis and tumor progression in renal cell carcinoma. Methods: Quantitative real-time reverse-transcribed polymerase chain reaction was applied to measure relative GATA1 mRNA expression levels in 135 kidney tissue samples, including 77 clear cell RCC (ccRCC) tissues and 58 paired adjacent normal renal tissue samples. Relative GATA1 expression levels were determined using the ΔΔCt method. Results: The mean GATA1 expression levels were significantly decreased in tumor tissues compared to adjacent normal tissues (p &lt; 0.001, paired t-test). In univariate logistic regression analysis decreased GATA1 mRNA expression was associated with advanced tumor disease (p = 0.005), positive status of distant metastasis (p = 0.03) and lymph node metastasis (p = 0.011). Reduced GATA1 expression was associated with an increase risk of disease recurrence (p = 0.005, hazard ratio HR = 0.05). Status of distant metastasis remained also a significant independent parameter in the bivariate Cox regression model (p = 0.05, HR = 3.01). Conclusions: GATA1 mRNA expression is reduced in ccRCC and associates with a poor clinical outcome and worse clinicopathology, indicating a possible role of GATA1 in tumor development and aggressiveness of ccRCC. GATA1 could therefore serve as a new biomarker for tumor progression in ccRCC.
Adding cisplatin to an anthracycline-based primary chemotherapy in triple-negative (TN) and non-triple negative (non-TN) T4 breast cancer patients (pts): Long-term outcomes
Authors: M. Ionta, F. Atzori, M. Murgia, B. Frau, M. Barca, A. Coinu, A. Trogu, F. Eltrudis, L. Minerba, B. Massidda
Journal: Journal of Clinical Oncology (2009)

583 Background: Clinical data demonstrated that standard anthracycline-based chemotherapy may be less beneficial in TN. Conversely, there is extensive preclinical work showing that TN tumors are highly sensitive to platinum agents. Only a few studies compared cisplatin vs non-cisplatin containing regimens among TN or non-TN homogeneous populations. The aim of this study was to evaluate the efficacy in terms of long-term outcomes of adding cisplatin to an anthracycline-based neoadjuvant regimen (cisplatin, C) compared with a standard anthracycline-based (Non-C) regimen in T4 breast cancer according to TN or non-TN status. Methods: We retrospectively analyzed 125 consecutive T4 breast cancer pts available for ER/PR and HER2 status; 98 pts (80%) were non-TN, of whom 63 treated with Non-C and 35 treated with C regimen; 27 pts (20%) were TN, of whom 10 treated with Non-C and 17 treated with C regimen. All pts received CMF, RT and hormone-therapy if indicated as adjuvant setting. None of the HER2 positive pts received peri-operative trastuzumab. Results: At a median follow-up of 101 months (8–217), estimated 10-year DFS and OS in TN pts treated with C were 47% and 59% versus 10% and 30% in pts treated with Non-C. In non-TN pts DFS and OS were 57% and 70% in pts treated with C versus 37% and 49% in pts treated with Non-C. Conclusions: Our data suggest that both TN and non-TN pts derive a better outcomes from the add of cisplatin over a standard anthracycline-based regimen. Of note, the magnitude of the benefit of cisplatin appears greater in the TN group. In order to validate these findings large prospective randomized trials are warranted. [Table: see text] No significant financial relationships to disclose.
Long-term results of MRI-guided partial prostate brachytherapy for favorable-risk prostate cancer: Implications for focal therapy.
Authors: Paul Linh Nguyen, Ming-Hui Chen, Yuanye Zhang, Clare M. Tempany, Robert A Cormack, Clair Beard, Mark D Hurwitz, W. Warren Suh, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2012)

114 Background: To report long-term results of MRI-guided partial prostate brachytherapy and propose a definition of biochemical failure following focal therapy Methods: From 1997-2007, 318 men with cT1c, PSA &lt; 15, Gleason ≤ 3 + 4 prostate cancer received MRI-guided brachtherapy in which only the peripheral zone was targeted. To exclude benign PSA increases due to prostatic hyperplasia, PSA failure was defined as nadir + 2 with PSA velocity &gt;0.75 ng/mL/year. Cox multivariable analysis was used to determine factors associated with PSA failure. Results: After a median follow-up of 5.1 years (interquartile range: 2.8 to 7.3, maximum 12.1), 26 men failed. While 36 patients met nadir+2 criteria, all eight biopsy-proven local recurrences were among the 26 men who also had a PSA velocity &gt;0.75 ng/mL/year. On multivariable analysis, having intermediate vs. low-risk disease (adjusted HR: 4.4 [95%CI: 1.3-5.5], p&lt;0.001) was the only factor significantly associated with an increased risk of PSA failure. PSA failure-free survival at 5 and 8 years was 95.6% and 90.0% for low risk, and was 73.0% and 66.4% for intermediate risk, respectively. Conclusions: MRI-guided brachytherapy targeting the peripheral zone produced comparable cancer control rates to whole-gland treatment in men with PSA-detected low-risk disease, but may not be adequate for men with “favorable” intermediate-risk disease. Requiring a PSA velocity&gt;0.75 in addition to nadir+2 may be a more appropriate way to define biochemical failure after therapies that target less than the whole gland.
Feasibility assessment of GI tumor stroma gene expression profiles with microarray technology in formalin-fixed, paraffin-embedded (FFPE) specimens.
Authors: S. X. Wang, J. Wang, M. S. Beg, E. Ozhegov, A. X. Qu, V. Bogdanov
Journal: Journal of Clinical Oncology (2011)

232 Background: Cancer stroma plays a critical role in tumorigenesis. Microarrays are widely used to study gene expression patterns in tumor frozen tissue to explore tumorigenesis and predict recurrence. Here we explored the feasibility of applying microarrays to tumor stroma using FFPE specimens. Methods: Ten samples were obtained from one colon and one pancreatic cancer specimen. Tumor stroma and normal stroma were microdissected. RNA was extracted, amplified, and labeled using Nugene FFPE kit, with array analysis using Affymetrix Human Gene 1.0. To assess reproducibility, each stroma sample was run twice in parallel. To test the reproducibility of sampling, the specimen was microdissected twice at a different stroma location. GenePattern software was used; correlation between parallel samples and the repeat dissection samples was calculated and ComparativeMarkerSelection program with two-sided T test was used to study gene profiles in pancreatic and colon stroma. To validate the array results, the profile differences were analyzed against public databases. Results: The correlation between the duplicate samples was in the range of 0.978-0.988. The correlation between the original versus the repeat dissection at a different stroma site was 0.953-0.967. 19,319 probes with gene annotation were examined, and pancreatic stroma was compared to colon stroma. We found that 90% of these genes were expressed at similar levels. Using a cutoff of 1.3, we identified 50 genes that were expressed greater than 30% in pancreatic stroma compared to colon stroma. We researched these 50 genes against GeneNote, GNF, Unigene and SAGE databases. Upregulation of 95% of these genes in pancreatic stroma is consistent with the public databases. Moreover, among these genes we identified PNLIP, CPB1 CPA2, PRSS1/PRSS2, AMY1A, AMY1B, AMY1C, and AMY2A, known to be highly expressed in pancreatic tissue. Conclusions: Gene expression microarray is a tool that can be effectively used to analyze normal and tumor stroma in GI cancer. FFPE tissue is suitable for such an analysis, as evidenced by high reproducibility and biologic consistency of the obtained data. No significant financial relationships to disclose.