tbuckley/cabot-search huggingface dataset:
Association of CD20 positivity (+) with event free survival (EFS) in children with post-transplant lymphoproliferative disease (PTLD) following solid organ transplantation (SOT)
Authors: M. Orjuela, B. Alobeid, E. R. Kott, L. J. Addonizio, S. J. Lobritto, A. L. Siebert, E. Morris, J. H. Garvin, M. S. Cairo
Journal: Journal of Clinical Oncology (2007)

8070 Background: The roles of CD20 and EBV as prognostic features for development and survival of pediatric PTLD after SOT are poorly understood. We previously demonstrated the safety and efficacy of cyclophosphamide, prednisone and rituximab (CPR) in CD20+ PTLD (Orjuela/Cairo, CCR 2005) Methods: All patients (pts), =25 yrs with PTLD in the past 15 yrs were analyzed and classified according to presence of detectable EBV or CD20 by IHC or ISH. Overall survival (OS) and EFS were estimated using Kaplan-Meier, significance was assessed by t-test comparison and Mantel-Cox. Results: 41 SOT pts (28 heart, 8 liver, 4 kidney) had PTLD (53.6% female) at a median of 38.8 months (mo) post SOT (4–43); Age 14–263 mo. Of 35 evaluable tumors, 29 (82.9%) had detectable EBV, while 22 (62.9%) expressed CD20 antigen. All pts had immunosuppression reduced, followed by chemo- and immunotherapy as needed. In pts with =9 mo follow-up after PTLD (n = 38) (median 49 mo, 10–184) OS is 73.2% and PTLD related EFS is 63%. Pts with EBV+ tumors had a shorter time to onset than those with EBV- tumors (median 18 vs 44 mo, p = 0.002). Pts with CD20+ PTLD were diagnosed earlier than those with CD20- PTLD (median 19 vs 62 mo, p= 0.006). PTLD-related 5 yr EFS showed significantly increased survival for CD20+ over CD20- pts (90 ± 6.5% vs 25 ± 11.2%, respectively [95% CI], p = 0.001). EBV status did not have a significant effect on OS (p=0.7) or EFS (p=0.7). Conclusions: CD20 and EBV are important predictors of time to PTLD development and presence of CD20 predicts for significantly improved EFS for SOT PTLD. CD20- PTLD pts appear to have lower EFS suggesting a need for alternative treatment strategies. No significant financial relationships to disclose.
JAK2 exon 14 Skipping in Patients with Primary Myelofibrosis (PMF),
Authors: Paolo Catarsi, Vittorio Rosti, Vittorio Abbonante, Alessandra Balduini, Gaetano Bergamaschi, Elisa Bonetti, Valentina Poletto, Laura Villani, Giovanni Barosi
Journal: Blood (2011)
Bortezomib (Velcade) in the Treatment of Relapsed or Refractory Multiple Myeloma: Analysis of Safety and Efficacy of Bortezomib From Registry of Monoclonal Gammopathy of Czech Myeloma Group
Authors: Viera Sandecka, Ivan Spicka, Vladimir Maisnar, Tomas Pika, Evzen Gregora, David Starostka, Lenka Walterova, Jaromir Gumulec, Dagmar Adamova, Marek Wrobel, Ivan Vonke, Lenka Zahradova, Jan Straub, Jakub Radocha, Jiri Minarik, Petr Pavlicek, Petr Kessler, Ludek Pour, Roman Hajek
Journal: Blood (2012)
Factors influencing recurrence in long-term survivors with early-stage breast cancer of low risk.
Authors: Xerxes Pundole, E. Susan Amirian, Patricia Thompson, Abenaa M. Brewster, Melissa Bondy
Journal: Journal of Clinical Oncology (2014)

597 Background: Approximately 60% of women with breast cancer (BC) are diagnosed with early stage disease with 5-year survival rates estimates of 84.4% to 98.6% depending on tumor type and extent of lymph node involvement. Despite high survival rates, many women experience recurrences after 5, 10 and even 15 years. Little is known about the influence of lifestyle and other 'host' factors and disease recurrence in 'long-term' survivors with low-risk disease. Methods: A retrospective case-only study of stage I-II BC patients, at The University of Texas M.D. Anderson Cancer Center from January 1, 1985 to December 31, 2000. The cases were disease free 5 years from diagnosis, and for whom baseline and follow-up information were available. We sought to compare epidemiologic and clinical factors among patients that had a late recurrence of their primary BC to those who did not. Results: A total of 2,468 patients were included in the original study from 1985 to 2000, of these 2,047 (83%) women were followed for >5 years. We obtained epidemiologic information on 1,057 (52%) women, of which 1,035 (98%) women were disease free and 22 (2%) had a recurrence after 5 years of being disease free. Multivariable analysis revealed that Hispanic women [Reference (Ref) Caucasian, (odds ratio (OR), 3.78, p =0.02] and heavy alcohol drinkers [Ref never drinkers, OR, 11.2, p=0.00] were significantly associated with recurrence in these patients with low risk disease, after adjusting for the year of diagnosis. No other clinical or histopathological characteristics at diagnosis or other epidemiologic factors (BMI, smoking, family history) were associated with recurrence in this sub cohort. Conclusions: Though limited by inherent bias of non-inclusion of women lost to follow-up and a small sample size, to our knowledge, this is the first evidence suggesting that alcohol consumption may increase the risk of late recurrence in an otherwise good prognosis group. Our results contrast published findings of no overall main effect of alcohol at baseline as a risk factor for BC recurrence and suggest a need to test the effect of alcohol consumption on late recurrence, where tumor biology is less likely to overwhelm modest but significant effects of lifestyle factors.
TIGER 1: A randomized, open-label, phase 2/3 study of rociletinib (CO-1686) or erlotinib as first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC).
Authors: D. Ross Camidge, Juergen Wolf, Jason B. Litten, Linda A Higashi, Jeffrey D. Isaacson, Tony Mok
Journal: Journal of Clinical Oncology (2015)

TPS8108 Background: Activating EGFR mutations including exon 21 L858R and exon 19 deletions (del19) are key drivers of NSCLC in 10%–15% of patients (pts) of European and 30%–35% of Asian descent.1 Acquired resistance (AR) to first-generation EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib is driven by additional EGFR mutations, with exon 20 T790M accounting for 60%–70% of cases.2 Rociletinib (CO-1686) was designed to inhibit T790M as well as L858R and del19 while sparing wild-type EGFR and has demonstrated response rates up to 67% and is well tolerated in pts with AR to EGFR-TKIs during dose-finding studies.3TIGER 1 will evaluate whether rociletinib can improve progression-free survival (PFS) in the first-line setting. Novel exploratory endpoints include tumor kinetics, treatment post-progression, circulating tumor DNA, and blood-based biomarkers. Methods: Pts with histologically or cytologically confirmed metastatic or unresectable locally advanced recurrent NSCLC (no prior EGFR TKI therapy and no CNS disease), with documentation of ≥ 1 activating EGFR mutation (excluding exon 20 insertions) will be enrolled in this phase 2, open-label study (NCT02186301). Pts will be randomized 1:1 to rociletinib (625 mg) twice daily or erlotinib (150 mg) once daily until disease progression according to RECIST 1.1. Pts will be stratified by sensitizing EGFR mutation (T790M, del19, L858R, or other) and race (Asian vs non-Asian). The primary endpoint is PFS; secondary endpoints include efficacy as determined by objective response rate, duration of response, disease control rate and overall survival, and PFS in pts with baseline T790M mutations detected using allele-specific PCR. PFS and OS will be summarized with Kaplan-Meier plots. The stratified log-rank and hazard ratio will compare PFS distributions for rociletinib- vs erlotinib-treated pts. Safety will be assessed via standard adverse event reporting. Planned enrollment is for phase 2 is 200 pts up to 1000 for phase 3. Enrollment is underway with multiple patients in screening. Herbst R et al. N Engl J Med. 2008 Yu H et al. Clin Cancer Res. 2013 Sequist LV J Clin Oncol. 2014 Clinical trial information: NCT02186301.
Phase II efficacy results using an oncolytic herpes simplex virus (NV1020) in patients with colorectal cancer metastatic to liver (mCRC)
Authors: S. K. Geevarghese, A. Chen, D. A. Geller, H. A. de Haan, A. Iagaru, A. Knoll, J. Nemunaitis, T. R. Reid, D. Y. Sze, K. Tanabe
Journal: Journal of Clinical Oncology (2009)

4089 Background: NV1020 is a genetically engineered oncolytic Herpes virus. Published Phase 1 dose-ranging results reported no significant related toxicity except for a mild (&lt;24 hr) viral syndrome. Initial Phase 2 tumor response data using the optimal biological dose (OBD) are now presented. Methods: Patients with heavily pretreated, progressing liver mCRC received 4 doses of NV1020 (1 X10 8 pfu) by weekly hepatic artery infusion followed by two cycles of conventional chemotherapy. Follow-up (≥1 year) evaluation included 4 X 3-monthly scans, then telephone contact to determine survival. Blinded, independent radiologists interpreted CT (modified RECIST) and FDG PET (EORTC) scans. Results: All 22 patients had prior 5FU-based treatment: 77% and 58% also had oxaliplatin or irinotecan, respectively (50% both agents); 86% had one targeted therapy (24% ≥2 such agents); 29% had radiofrequency ablation. Mean time from primary resection was 95 weeks, mean CEA was 182 ng/mL, and 55% had pulmonary lesions. Two patients received only 2 NV1020 infusions due to rapidly progressing disease. Virus tolerability was unchanged from Phase 1 and no related, serious or Grade 4 toxicity was found. NV1020 neutralizing antibodies rose in all patients but no NV1020 was shed (saliva, skin). After NV1020 alone, 10/22 (45%) and 8/20 (40%) on CT and PET, respectively, showed stable disease. 21 patients subsequently received chemotherapy, 45% with drugs to which they were previously refractory and 36% with only one new drug. 14% refused both planned cycles. Best response observed with CT was 55% (1 CR, 1 PR, 10 SD) and 59% (5 PR, 8 SD) with PET. Despite intrahepatic delivery, some remote responses were observed. Response did not correlate with initial tumor size, SUV, or CEA, with time since primary resection, pre- or post NV1020 chemotherapy type. Nine (41%) remain alive &gt; 1 year. Kaplan-Meier median time to progression is 28 weeks (95% CI [9–37]); median survival probability is 52 weeks (95% CI [36–90]). Conclusions: NV1020 stabilizes liver metastases in highly advanced mCRC and may sensitize tumors to salvage chemotherapy resulting in extended overall survival. A controlled Phase 2/3 trial is justified. [Table: see text]
Young patients and gastrointestinal (GI) tract malignancies: Are we addressing the unmet needs?
Authors: Gali Perl, Sharon Nordheimer, Shany Lando, Baruch Brenner, Shlomit Perry, Graciela Shmoisman, Limor Amit, Salomon M. Stemmer, Irit Ben-Aharon
Journal: Journal of Clinical Oncology (2015)

e20598 Background: Recent epidemiological studies indicate the rate of GI malignancies among younger population is constantly increasing, mainly due to colorectal cancer. There is paucity of data regarding the magnitude of treatment-related symptoms, psychosocial issues and potential unmet needs in this population. Our study aimed to characterize the needs and elucidate whether it might be amenable to potential intervention. Methods: Female and male patients who were diagnosed with cancer of the gastrointestinal tract before the age of 40 y and were treated at our institute were asked to complete a questionnaire (consisted of modules according to SF-12 and CARES validated questionnaires). Measures of symptoms, daily function and unmet needs were evaluated. Results: Fifty patients were enrolled into the study, gender ratio was 1:1. Median age at diagnosis was 36.5y (21-40y). The symptoms that were significantly prevalent during and after treatments compared with baseline status were: diarrhea (37% post treatment), sleeping disorder (32% post treatment) and sexual dysfunction (31% post treatment; p < 0.05). In the psychosocial function module, patients reported significant impairment in occupational activities, coping with children and relationship with spouse (p < 0.05). Patients reported significant unmet needs for nutritional counseling and psychosocial support (p < 0.05), other needs as occupational counseling, spiritual support, financial counseling and palliative support were not found to be unmet. Patients who were treated with multimodality treatment (surgery, chemotherapy and radiation) presented higher rates of unmet needs (76% vs 48%; p-0.03). Conclusions: Young patients with GI cancers represent a group with unique characteristics and needs compared with published evidence on other young-onset malignancies. The distinctive symptoms, areas of treatment-related functional impairments indicate there are unmet needs, especially in the area of psychosocial support and nutritional counseling.
Phase II double-blind placebo-controlled study of armodafinil for brain radiation induced fatigue.
Authors: Edward G. Shaw, Doug Case, David Bryant, David Grisell, Glenn Lesser, Drew C. Monitto, Michelle Joy Naughton, Stephen R. Rapp, Steven R. Savona, Sunjay Shah, Michael D Chan
Journal: Journal of Clinical Oncology (2013)

9505 Background: Armodafinil (ARM), the R-enantiomer of modafinil, is FDA approved for narcolepsy, shift work disorder, and treated sleep-apnea, and has also been shown to reduce fatigue/improve cognitive function in cancer patients. This phase II study estimated the efficacy and toxicity of ARM in primary brain tumor (PBT) patients receiving brain radiation therapy (RT) to determine whether a larger phase III study would be warranted. Methods: Eligibility criteria – adult, PBT, total RT dose &gt;45Gy, KPS&gt;60, no severe headaches, and concurrent chemotherapy allowed. Patients were assessed at baseline, end of RT, then 4 weeks after end RT with the Brief Fatigue Inventory (BFI), Epworth Sleep Scale (ESS), FACT, and FACT brain and FACIT fatigue subscales. Patients were randomized to receive ARM 150mg/day during RT and for 4 weeks after RT or placebo (PLAC). Results: 54 patients enrolled between 9/10-12/12; 26 to ARM, 28 to placebo PLAC. Median age 59; 59% female; 95% White; 41% KPS 90-100, 59% KPS 60-80; 74% malignant glioma, 26% low-grade glioma/benign histology. 83% patients had concurrent chemotherapy. For all randomized patients, there were no statistically significant differences in outcome between ARM and PLAC groups at end-RT vs. baseline or 4 weeks post RT vs. baseline. For patients who had more baseline fatigue (fatigue subscale score &lt;median), ARM-treated patients had significantly/suggestively better outcomes at end-RT vs. baseline compared to PLAC-treated patients: less fatigue (BFI p=0.056, fatigue subscale p=0.0295), less sleepiness (ESS p=0.1034), and better QOL (FACT p=0.0001). Incidence of grade 2/3 toxicities was the same between the two treatment groups: 7% anxiety, 7% nausea, 18% headaches, and 20% insomnia. There were no grade 4 or 5 toxicities. Conclusions: In irradiated PBT patients, fatigue, sleepiness, and reduced QOL occurring at the end of brain RT was less with ARM in those patients who were more fatigued at baseline. Toxicity was minimal. These data support conducting a larger phase III study. Analysis of cognitive function data is ongoing. Support - NIH/NCI grant 2U10 CA 81851 and Teva Pharmaceuticals. Clinical trial information: 95709.
A nomogram for individually predicting the 5-year postoperative recurrence probability in T1 to T2 node negative (T1, 2N0) non-small cell lung cancer.
Authors: Wenhua Liang, Wenlong Shao, Hui Pan, Qiuhua Deng, Xiaoshun Shi, Daoyuan Wang, Jianxing He
Journal: Journal of Clinical Oncology (2014)

e18534 Background: It is still controversial whether non-small cell lung cancer (NSCLC) patients with pathologically lymph node (LN) negative disease (N0) should receive adjuvant chemotherapy. Some features were considered high risk factors for recurrence in T2 disease and probably in T1 disease. Therefore, we sought to quantify the impact of these clinical factors on recurrence and to develop a nomogram for predicting and illustrating the individual 5-year recurrence probability. Methods: A Chinese multi-institute registry (2001-2008) of 6111 consecutive NSCLC patients who had undergone radical resection was used to screen eligible patients (T1-2, N0, follow-up for disease recurrence). Genders, age, ECOG performance status, histology, tumor location/differentiation/greatest diameter, visceral/pleural invasion, operation types and sampled LN counts were examined. Multivariate logistic regression model were used to identify significant variables and integrate them into the nomogram. Bootstraps with 1,000 resample were used for calibration and calculating the concordance index (C-index). Results: A total of 366 patients were eligible for analysis. Tumor differentiation (poor vs. well/moderate, OR=1.578, P=0.049), tumor diameter (≥4cm vs. <4cm, OR=2.070, P=0.002), operation type (wedge vs. non-wedge resection, OR=25.723, P=0.002) and Nx (sampled LN<14 vs. sampled LN≥14, OR=3.015, P<0.001) remained significant factors in multivariate model and were built into the nomogram. The C-index of the nomogram was 0.70 (0.65, 0.76), which outperformed any single factor (tumor differentiation 0.56, diameter 0.59, operation types 0.53, Nx 0.61). After being bisected, patients in high-risk group (score>33) were associated with greater 5-year recurrence probability compared with low-risk group (scored 0-33) (63.4% vs. 35.0%, P<0.001) which was the same in stage IA subgroup (70.8% vs. 39.0%, P=0.009). Conclusions: Tumor differentiation, size, operation type and Nx could predict high risk for recurrence. A nomogram incorporating these factors could optimize the prediction and patient stratification.
The impact of the Affordable Care Act on treatment of testicular cancer.
Authors: John Joseph Francis, Robert Abouassaly, Christopher Gonzalez, Neal J. Meropol, Alexander Kutikov, Marc C. Smaldone, Sarah P. Psutka, Stephen Bentley Williams, Simon P. Kim
Journal: Journal of Clinical Oncology (2017)

422 Background: The passage of the Affordable Care Act (ACA) in 2010 aimed to improve access for uninsured patients to private health insurance. Yet, the impact of the ACA on the number of privately insured young patients and on the timeliness of medical care for serious medical conditions, remain unclear. Thus, we sought to ascertain changes in insurance status and evaluate timeliness of post-orchiectomy definitive therapy for young men diagnosed with testicular cancer following passage of the ACA. Methods: From the National Cancer Database, we identified all patients 18 – 50 years of age diagnosed with stages I – III testicular cancer from 2007 to 2013. Patients were divided into groups at the time of diagnosis; 2007 – 2009 (pre-ACA) and 2011 to 2013 (post-ACA). Only patients who had undergone radical orchiectomy and had a reported insurance status were included in analysis. The primary outcomes were insurance type at diagnosis and time to treatment of secondary therapy following orchiectomy (systemic chemotherapy, radiation therapy, or surgery {Retroperitoneal lymph node dissection; RPLND}). Results: Overall, 17,945 patients were included in analysis with 53.5% diagnosed with pure seminoma and 46.5% diagnosed with nonseminomatous germ cell tumor (NSGCT). In comparing pre- and post-ACA cohorts, the percentage of patients with private health insurance decreased following the passage of the ACA (74.1% vs. 71.2%; p &lt; 0.01). Similarly, the percentage of patients without any insurance increased between the two time frames (12.7 % vs. 13.4%; p &lt; 0.01). More patients presented with clinical stage II and III disease following the passage of the ACA (28.9% vs. 31.9%; p &lt; 0.01). Compared to patients without health insurance, privately insured patients received more timely secondary definitively therapy with radiation therapy (49.9 vs. 60.9 days, p &lt; 0.01) and chemotherapy (41.5 vs. 45.7 days, p &lt; 0.01) but no difference in the time to RPLND (18.8 vs. 16.7 days, p = 0.70). Conclusions: The impact of the ACA on patients with testicular cancer shows minimal worsening in the number of privately insured young men and increasing rates of advanced testis cancer. This was not in agreement with our hypothesis and suggests the ACA is not benefiting young men with this malignancy.
Ascending dose trials of the safety and tolerability of Toca 511, a retroviral replicating vector encoding cytosine deaminase, in patients with recurrent high-grade glioma.
Authors: Daniel Pertschuk, Timothy Francis Cloughesy, Susan Marina Chang, Manish K. Aghi, Michael A. Vogelbaum, Linda M. Liau, Bob B. Shafa, William H. Yong, Clark Chen, Santosh Kesari, Carlos E. Ibanez, Omar D. Perez, Joan M. Robbins, Douglas J. Jolly, Harry E. Gruber
Journal: Journal of Clinical Oncology (2012)

2101 Background: Patients with the most common and aggressive form of brain cancer, glioblastoma multiforme (GBM), have a poor prognosis and current treatments are only palliative. Gene therapy approaches using replication-deficient viral vectors have been investigated previously for GBM with limited efficacy, likely due to poor gene delivery throughout the tumor. Methods: Toca 511 is a novel retroviral replicating vector (RRV) that is engineered to deliver a modified cytosine deaminase prodrug activator gene (CD) selectively to cancer cells. In those cancer cells expressing the CD gene, the antifungal prodrug 5-FC is converted to 5-FU. We are currently evaluating the safety and tolerability of a single dose of Toca 511 administered by direct intratumoral injection to subjects with recurrent high grade glioma (rHGG). After a period of time during which the vector is allowed to spread through the tumor, the patient begins oral 5-FC which is repeated cyclically. Results: Three subjects have been enrolled in each of the first two dose groups. No dose limiting toxicities (DLTs) have been identified in these groups and the treatment was well tolerated. There have been no grade 3 or 4 AEs considered related to either Toca 511 or 5-FC. A further 9 subjects were then enrolled at the 3rd dose level and are being followed. A second study has been initiated in which Toca 511 is injected into the walls of the resection cavity at the time of surgery for rHGG and followed by cyclic treatment with oral 5-FC. Conclusions: These clinical studies are the first to investigate a RRV to deliver genes to human brain tumors and further dose escalation is anticipated.