tbuckley/cabot-search huggingface dataset:
A phase I trial of a yeast-based therapeutic cancer vaccine targeting CEA.
Authors: R. A. Madan, M. Bilusic, J. W. Hodge, K. Y. Tsang, P. M. Arlen, C. R. Heery, M. Rauckhorst, S. McMahon, C. Intrivici, T. A. Ferrara, A. Cohn, D. Apelian, A. Franzusoff, Z. Guo, J. Schlom, J. L. Gulley
Journal: Journal of Clinical Oncology (2011)

2604 Background: Saccharomyces cerevisiae (yeast) were engineered to express human CEA protein and administered as a heat killed, whole yeast therapeutic vaccine. Preclinical studies have shown that these modified yeast can induce a strong immune response to CEA as well as antitumor responses in a CEA-transgenic host. Methods: Patients (pts) were enrolled in this classic phase I design at 3 dose levels: 4, 16, and 40 yeast units (each unit =107 yeast particles). The vaccine was administered in equal doses at 4 sites subcutaneously in bilateral inguinal and anterior chest wall regions. Vaccine was administered at 2 week intervals for 3 months, then monthly. Eligible patients were required to have a serum CEA > 5 ng/ml or >20% CEA+ positive tumor block, ECOG PS 0-2, and no autoimmune history. An expansion cohort of 10 ECOG PS 0-1 pts was enrolled to focus primarily on immune response at the 40 yeast unit dose. Pts had re-staging scans at 3 months, then bimonthly. Peripheral blood was collected for analysis of immune response. Results: A total of 25 pts have enrolled. The most common adverse event (AE) is grade 1/2 site reaction (no grade ≥3 attributable AE). Most pts were heavily pre-treated with advanced disease where vaccine-induced immune response can be difficult to generate. Of 22 evaluable pts, 4 pts (3 colon and 1 medullary thyroid cancer) had stable disease beyond 3 months and 2 are on-going (3+, 5, 7, 8+). All 4 of these pts had declines or stabilization in serum CEA after treatment with vaccine was initiated. Immunologic analysis is ongoing. Conclusions: A yeast-based vaccine targeting CEA has demonstrated safety and a subset of patients showed stable disease beyond 3 months. Immunologic activity is being evaluated and a study in medullary thyroid cancer pts with rising tumor markers is being planned.
Comparison of immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) to determine the presence of Gen HER-2Neu in breast carcinoma
Authors: A. E. Borello, L. Figueroa, A. Basquiera, P. Calafat, A. Diller, A. E. Sturich, N. Rossi, J. J. García, E. Palazzo
Journal: Journal of Clinical Oncology (2008)

11567 Background: The amplification of gen Her-2 and the concomitant overexpression of the transmembrane protein is found in 15–25% of breast carcinomas. The determination of Her-2 expression is important to predict response to trastuzumab and anthracycline therapy and resistance to tamoxifen. We intended to analyze the concordance between the determination of Her-2 by IHC and FISH in our Institution. Methods: One hundred and nineteen FISH determinations were performed between April 2004 and September 2007 in patients of out cytogenetics lab with diagnosis of breast cancer. The IHC results were performed in different centers with diverse work methodology; the FISH were all performed by the same operator of our Institution. We had results of both techniques in 89 patients; in 24 cases, both studies were performed in patients of our Institution. For IHC, we used polyclonal antibody DAKO A0485 (avidine biotine peroxidase technique), semiquantitative score (0, 1, 2 and 3). For the gene amplification with FISH we used the PATH VYSION KIT, ABBOT Molecular INC (60 average cells per patient were analyzed). For the majority of the patients, we used material from the primary tumor and less frequently, from metastatic lesions or the local recurrent site. Results: In the total analyzed sample (n=89), the detection of Her-2 with IHC revealed a result of 0 in only 1 patient, 1+ in 3 patients, 2+ in 60 patients (67%) and 3+ in 25 patients (28%). The detection of gene amplification with FISH was uncertain in the only patient who had IHC: 0, negative in the 3 patients 1+. The positivity of FISH in cases 2+ was 31.67% (19/60) and in the 3+ was 76% (19/25). However, if we analyzed separately the results obtained in 24 patients in which both techniques were performed in our Institution, the detection of Her-2 with IHC revealed a result 1+ in only 1 patient, 2+ in 12 cases and 3+ in 11 patients (4.2%, 50% and 45.8%, respectively). The detection of gene amplification with FISH resulted negative in the only case 1+ by IHC (0/1). The positivity of FISH in cases 1+ was 25% (3/12) and in those 3+ was 90% (10/11). Conclusions: The concordance between IHC and FISH is higher if both determinations are performed following international standards and performed by co-working operators. No significant financial relationships to disclose.
Response to systemic therapy in non-clear cell renal cell carcinomas: A systematic review and meta-analysis.
Authors: Francisco Emilio Vera-Badillo, Arnoud Templeton, Alberto Ocana, Paulo deGouveia, Priya Aneja, Jennifer J. Knox, Ian Tannock, Ignacio Duran, Bernard J. Escudier, Eitan Amir
Journal: Journal of Clinical Oncology (2014)

425 Background: Clinical data supporting the efficacy of systemic therapy in non-clear cell renal cell carcinoma (non-ccRCC) are limited and based on retrospective analyses, expanded access programs and single arm phase II trials. Therefore the optimal treatment for this subgroup remains uncertain. Methods: A systematic review of electronic databases was conducted to identify publications evaluating the outcomes of patients with non-ccRCC (excluding those with sarcomatoid tumors) treated with different systemic approaches (immunotherapy, chemotherapy, targeted agents, small molecules). The primary endpoint was response rate and secondary endpoints were median progression free (PFS) and overall survival (OS). Where possible, data were pooled in a meta-analysis using the Mantel-Haenszel random-effect modeling. For studies comprising of unselected patients, outcomes of those with non-ccRCC were compared with clear cell renal cell carcinoma (ccRCC). Results: Forty-nine studies comprising 7,799 patients were included: 471 patients were enrolled on studies conducted exclusively in non-ccRCC and 7,328 patients on studies of unselected renal cell carcinoma. Among these, 903 (12%) had non-ccRCC and 6,425 (88%) had ccRCC. For non-ccRCC, overall response rate, median PFS and median OS were 9%, 7.9 and 13.4 months, respectively. By comparison, the overall response rate for ccRCC was 15% (Risk Ratio for response [RR] 0.67, 95% CI 0.52-0.86, p=0.002). This association was independent of type of treatment administered. Among the different novel agents (bevacizumab, lenalidomide, linefanib, sorafenib, sunitinib, pazopanib, everolimus and temsirolimus), sunitinib was significantly less efficacious in non-ccRCC than ccRCC (RR 0.56, 95% CI 0.42-0.72), but there was no significant difference in response rates for sorafenib (RR 0.64, 95% CI 0.31-1.35) or other agents (RR 1.10, 95% CI 0.50-2.44), However, confidence intervals were wide. Results of further analyses will be presented at the meeting. Conclusions: Patients with non-ccRCC have lower response rates than those with ccRCC, but the absolute difference between them is modest. Further study of targeted therapy in non-ccRCC is warranted.
Use of an EMR online portal for communication with cancer patients.
Authors: Craig Stephen Siegel, Vicky Spies, Miriam B. Rodin, Yifan Tu
Journal: Journal of Clinical Oncology (2016)

147 Background: Communication with patients about their health care is vital to the physician-patient relationship. This is especially true in oncology where patients receive frequent diagnostic evaluations and their diseases are often active and evolving. In 2009, as part of “meaningful use”, Congress mandated the need to establish an electronic portal for patient communication. We studied factors associated with the use of our online patient portal. Methods: We performed a retrospective chart review of the use of our EMR online portal, MyChart. We assessed whether patients were informed of the existence of the portal and if they had activated and used it. We analyzed whether disparities in age, gender, rural or urban residence, or income impacted patients’ use of this feature. Results: Between January 1, 2014 and December 31, 2015, 1947 patients were seen in the Hematology Oncology Clinic at St. Louis University Hospital. 508 (26.1%) had activated and used MyChart and 1437 (73.9%) had not. Of 1437 patients who had not used MyChart, 110 (7.6%) had not been given the code, 1316 (91.5%) had been given the code but had not activated it, and 13 (0.9%) had declined the code. Patients who activated MyChart were more likely to be less than 65 years old (60.0% vs 40.0% p &lt; .0.0001). Patients who did not activate it were more likely to live in a ZIP code where the median annual income was below the state median, a surrogate for lower income (84.8% vs 15.2%, p &lt; 0.0001). Use of MyChart was not statistically associated with gender or with residence in an urban versus rural location. Conclusions: A large majority of patients in our urban, academic oncology clinic did not access the online communication portal. Use was associated with younger age, and lack of use was associated with residence in a lower income ZIP code. There was no association between use and gender or residence in an urban versus rural location. Future work will attempt to improve provider-patient communication through increasing access to the portal.
Impact of duration of neoadjuvant radiation on rectal cancer survival.
Authors: Aalok Kumar, Renata D'Alpino Peixoto, Hagen F. Kennecke, Caroline Speers, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2015)

682 Background: The utility of neoadjuvant radiation (XRT) for the treatment of stages II-III rectal cancer has been demonstrated previously. However, the optimal amount and duration XRT in this setting remains unknown. Using a population-based cohort of stage II and II rectal cancer (RC) patients treated with curative intent including XRT, our aims were to 1) examine the patterns in XRT use and 2) explore the relationship between XRT course and survival. Methods: We analyzed patients diagnosed with clinical stage II-III RC from 2006 to 2010 and treated with long course 45-50.4 Gray (LC) or short course 25 Gray (SC) XRT at any 1 of 5 regional cancer centers in British Columbia. Logistic regression models were constructed to determine the factors associated with the course of XRT given, LC vs. SC. Kaplan-Meier methods and Cox regression that accounted for known prognostic factors were used to evaluate the relationship between XRT course and disease-free (DFS), overall survival (OS), local recurrence free survival (LRFS) and distant recurrence free survival (DRFS). Results: 427 patients were identified: median age 65 years (range 31 to 94), 67% men, 87% T3/4 tumors, and 74% with N1 or N2 disease. Among them, 240 (56%) received SC and 187 (44%) received LC. Adjusting for confounders, patients with N1 or N2 disease were more likely to receive LC (OR for LC 5.08, 95% CI, 2.51-11.22, p&lt;0.0001 and 8.35, 95% CI, 3.35-22.39, p&lt;0.0001, respectively), while older age patients were less likely to receive LC (OR 0.95, 95% CI, 0.94-0.98, p&lt;0.0001). On univariate analysis, there was no significant difference seen in DFS, OS, LRFS, and DRFS between LC and SC. Similarly, in multivariate analyses comparing LC vs. SC, the course of XRT was not associated with differences in DFS (HR 1.06, 95% CI, 0.68-1.64, p=0.80), OS (HR 0.91, 95% CI, 0.61-1.37, p=0.66), LRFS (HR 0.79, 95% CI, 0.39-1.57, p=0.50) and DRFS (HR 0.99, 95% CI, 0.60-1.61, p=0.95). Additional baseline clinical and tumor characteristics did not influence outcomes (all p&gt;0.05). Conclusions: Appropriate pre-operative selection of SC vs. LC neoadjuvant XRT for early stage RC based on patient and tumor characteristics was not associated with differences in survival outcomes.
3 Steps 4 Health, a program on quality of life.
Authors: Ann Fonfa
Journal: Journal of Clinical Oncology (2015)

95 Background: As Patient advocates we have spent years gathering/ sharing information about simple, natural strategies to reduce risk of cancer treatment-related toxicities and strengthen the immune system. Methods: We created a simple 3 step program that absolutely anyone with cancer, at any stage, can incorporate into their own healthful protocol. Since it involves no tools and can be used at the level that an individual is at the time they start, we consider it appropriate for all. Further we cannot see any objection from the Oncologist or staff members. Step 1 is eating one more fruit and one more vegetable every day. This is helpful since studies show few Americans are getting enough fruits or vegetables. The National Cancer Institute considers ‘Five a Day’, a minimum. We want to get people started on the correct path simply and easily. Step 2 is taking a walk around the room, facility or neighborhood depending on ability and health status. This has been shown by many studies to help anyone with cancer, undergoing treatment or in recovery. We are not asking folks to become athletes; we are involving them in a plan to improve their health. Step 3: 7 deep breaths before treatment, in a stressful situation or at bedtime. This step is important to reduce stress and encourage relaxation. Results: Every step moves people forward into better health. We believe taking these first steps will lead to more healthful behaviors, better ability to handle conventional cancer treatments, and an easier recovery. Conclusions: Immune system health depends on the individual as much as any treatments. In this era of Immunology, we see a real opportunity for our Patient/Advocate-driven concept.
Acceptability among advanced cancer patients of creating legacy teaching videos.
Authors: Suzana Makowski, Amy Wachholtz, Christina Fitch, Alex Doering, Jennifer Tjia
Journal: Journal of Clinical Oncology (2015)

232 Background: The beneficial effects of life story review and legacy activities on the mood and quality of life for adults with advanced illness is well described, including the creation of legacy videos for family gifting. It is unknown whether creating legacy videos with the intent of teaching future healthcare professionals about the “cancer patient” experience is acceptable, beneficial, or meaningful to patients. The study aim is to describe the acceptability and success of recruiting patients with advanced cancer to create teaching videos for healthcare professionals. Methods: Patients aged 18 and older were recruited from the outpatient oncology clinic, palliative medicine clinic, and inpatient service of an academic medical center in the Northeast. Eligibility included having a diagnosis of an unresectable advanced cancer, an ECOG score of 0-3, being English speaking, and not having active psychosis. Patients underwent in-person, digital video recorded interviews that followed a semi-structured interview guide. Interview questions addressed the lived experience of being a “cancer patient,” coping, and how the patient thought clinicians could provide better care to future patients. For each patient, we measured the Functional Assessment of Cancer Therapy - General (FACT-G), Hospital Anxiety and Depression Scale (HADS), Patient Dignity Inventory (PDI), Distress Thermometer, and study acceptability. Results: Recruitment is ongoing. To date, of 12 patients referred, 4 completed the video, and 3 completed the follow-up visit. On average, it takes six contact attempts (phone calls or text message threads) to schedule an appointment that resulted in a completed video. Each interview lasted about a 1-1.5 hours. Patients reported that they “really enjoyed the experience,” and “it had helped them process” their cancer experience. A common theme was the patient’s strong desire to help others by sharing their story. Conclusions: Patients with advanced cancer find recruitment and participation in an educationally-oriented legacy video project acceptable and potentially personally helpful.
Loss of Non-Muscle Myosin Heavy Chain IIA Function Does Not Restrict Megakaryocyte Maturation or Spontaneous Platelet Release and Likely Affects Non-Cell-Autonomous Aspects of Thrombopoiesis.
Authors: Zhao Chen, Alessandra Balduini, Mary Anne Conti, Robert S. Adelstein, Ramesh A. Shivdasani
Journal: Blood (2006)
Epidemiology and survival of neuroendocrine tumors in Ontario: A 15-year population-based study.
Authors: Moises Cukier, Calvin Law, Ning Liu, Refik Saskin, Simron Singh
Journal: Journal of Clinical Oncology (2012)

184 Background: A recent study of the SEER database in the United States showed a 5-fold increase in neuroendocrine tumours (NETs) over the last 30 years. An increasing incidence has also been reported in Norway, Sweden, England, Holland, Italy and Japan, but interestingly not in Denmark and Switzerland. The objective of our study is to describe the incidence, anatomical distribution and survival of NETs in Ontario. Methods: A population based study was initiated using the Ontario Cancer Registry, cross-linked with the Registered Persons Database and the Canadian Institute of Health Information Discharge Abstract Database. All cases of NETs were identified in Ontario (&gt; 13 million persons) from 1994 to 2009. Baseline demographic, clinical and outcomes data were abstracted to allow for an analysis of annual incidence rates, and overall survival. Results: A total of N = 5619 cases were identified. The incidence rate increased from 2.46/ 100,000 (95% CI, 2.13-2.83) in 1994 to 5.86/ 100,000 (95% CI, 5.40 – 6.35) in 2009. The median age was 62 with 50.5% female cases. When divided by site, bronchopulmonary NETs where the most common (22%), then jejunum/ileum (17%) and rectal (16%) NETs, while pancreatic NETs (pNETs) and gastric NETs were 10% and 5% respectively. The absolute increase in the study period was most pronounced for pNETs (6-fold), rectal (5-fold) and gastric (5-fold) NETs. Metastatic disease was documented in 45% of the cases; 20% at diagnosis and 25% during follow-up. The 5-and 10-year overall survival (OS) was 61% and 46% respectively, for the entire population. Site specific 5-year OS were: rectal (87.0%), small bowel (73.4%), gastric (67.4%), colon (64.3%) and pancreas (48.8%). 5-year OS was compared for patients with and without metastatic disease after diagnosis (69.0% vs 40.1%, p&lt;0.0001). Conclusions: There appears to be a significant increase of reported cases of NETs in Ontario, Canada, particularly pNETs, rectum NETs and gastric NETs. This supports much of the population-based reports worldwide. Survival appears to vary significantly according to anatomical site and extent of disease. Further research is required to understand the impact of this cancer previously perceived to be rare but clearly increasing.
Panitumumab (Pmab) versus cetuximab (Cmab)/irinotecan (Iri) therapy among patients with KRAS wild-type (wt) metastatic colorectal cancer (MCRC).
Authors: Hagen F. Kennecke, Leo Chen, C. D. Blanke, Winson Y. Cheung, Kimberly Schaff, Caroline Speers
Journal: Journal of Clinical Oncology (2012)

640 Background: In British Columbia, use of anti-EGFR therapy for KRAS wt MCRC is limited to patients (pts) previously treated with both irinotecan and oxaliplatin. Physicians may choose either Pmab monotherapy or Cmab/Iri combination therapy. We sought to compare the characteristics and outcomes of all pts treated with Pmab/Cmab referred to 5 provincial cancer centers since July, 2009. Methods: Eligible patients received at least one dose of either Pmab (6mg/kg q2w) or Cetuximab (500mg/m2 q2w) plus Iri (180mg/m2 q2w). Baseline characteristics and systemic therapy were prospectively collected, while ECOG and metastatectomy status were retrospectively collected. Kaplan-Meier survival analysis was conducted from the first day of Pmab/Cmab. Results: Among 178 eligible pts, Pmab was chosen 3 times more often than Cmab/Iri (see table). Pts treated with Cmab/Iri were significantly younger and had better performance status than those treated with Pmab. There were no statistically significant differences in other prognostic variables, and a similar proportion received chemotherapy after Pmab vs. Cmab/Iri. Overall survival was slightly longer among patients receiving Cmab/Iri (8.3 mo), vs. Pmab (7.7 mo) (p=.03). Conclusions: Pmab was chosen more often than Cmab/Iri for similarly eligible patients. Cmab/Iri pts were younger, were more likely to have ECOG performance status 0/1 and achieved a modestly longer overall survival. Either regimen appears to be suitable for previously treated pts with KRAS wt MCRC. [Table: see text]
Genetic analysis of colorectal cancers in young patients.
Authors: Andrea M. Abbott, Nishi Kothari, Jamie K. Teer, Thejal Srikumar, Richard D. Kim, Damon R. Reed, David Shibata
Journal: Journal of Clinical Oncology (2015)

632 Background: The incidence of colorectal cancer (CRC) is increasing in adults &lt;50 years old and these cases may be associated with a worse prognosis. Despite our growing understanding of genetic conditions, a substantial number of CRC in young patients are classified as sporadic but may harbor unique molecular changes. We sought to compare profiles of genetic alterations between young and old patients who lack defects in known hereditary cancer genes. Methods: 283 CRC cases diagnosed between 1998 and 2010 were analyzed by targeted exome sequencing using the Illumina NGS platform with 50-100x coverage. Filtering of normal variants was performed using 1000 Genomes to enrich for somatic mutations which were then limited to those predicted to alter protein sequence. The younger and older cohorts were defined as ≤45 and ≥65 years old at diagnosis, respectively. Patients found to be MSI-high (n= 2 young, 50 old) or with a known hereditary syndrome (n=6) were excluded. For this preliminary screen, Fisher’s Exact test was used to detect differences in mutation frequencies. Results: A total of 195 older and 30 younger patients with median ages of 73 (range 65-93) and 42 (range 30-45) years respectively, were analyzed. We identified 57 genes with significant differential mutation frequencies. The top ten genes mutated with increased in frequency in the younger cohort are shown in Table 1. Conclusions: In this exploratory project, we identified mutations that occurred more frequently in younger CRC patients. Large scale validation of these findings and application of this approach may lead to novel screening and treatment strategies in younger patients [Table: see text]