tbuckley/cabot-search huggingface dataset:
Predictive value of Ile105Val polymorphism of the gluthatione-S-transferase P1 in patients with metastatic colorectal cancer (m CRC) treated with the triplet combination of irinotecan, oxaliplatin, and capecitabine
Authors: R. N. Zarate, J. Rodriguez, E. Bandres, N. Bitarte, N. Ramirez, M. Ponz, A. Chopitea, A. Viudez, J. Garcia-Foncillas
Journal: Journal of Clinical Oncology (2009)

2544 Background: Several phase I/II trials have shown that the triplet combination of oxaliplatin, irinotecan and capecitabine is a feasible and active in solid tumors. We aimed to investigate whether germline polymorphisms may be predictors of clinical outcome in mCRC pts treated with this combination. Methods: The following genetic polymorphisms were analysed: glutathione S-transferase (GSTP1-Ile105Val, GSTT1 and GSTM1 deletion), TYMS (TS-5´UTR 2R/3R; TS-5´G/C; TS-3´UTR 6-bp deletion), MTHFR 1298A&gt;C, UGT1A1, ERCC1, XPD. Polymorphisms from peripheral lymphocytes were detected using the TaqMan genotyping assays (Applied Biosystems, CA). Univariate analysis (Fisher´s exact test for response; log-rank test for TTP and OS) was performed to examine associations between polymorphisms and clinical outcome. Results: Blood samples for 63 out of 72 prospectively enrolled pts were tested for genomic analysis. Median age was 57 (32–78), median ECOG 1(0–2), median number of cycles administered 6 (1–13), median number of metastatic sites was 1 (1–4). M/F: 50/22. Risk according to Köhne classification was low (52.8% of pts), intermediate (26.4%) and high (8.3%). Overall response rate (ORR) was 62.5%. Median progression-free survival (PFS) was 9.87 months (95% CI; 7.6–12) and median overall survival was 24.6 months (95% CI; 19.5–29.7). A significant association was observed between MTHFR 1298A&gt;C and haematological toxicity, with C/C genotype pts being at higher risk of grade 3–4 neutropenia (50% vs. 28%, p = 0.035) and leucopenia (50% vs. 15%, p = 0.04). Heterozygous and homozygous GSTP-105Val showed a significant superior response rate (80%) compared to only 40% in pts harbouring the GSTP1–105Ile/Ile genotype (p = 0.008, Fisher´s exact test). PFS was also adversely affected in pts with GSTP1–105Ile/Ile (5.2 months vs. 12.3 months in those pts with at least one GSTP1–105Val allele, p = 0.001). In the multivariate analysis, the relative risk for progression was 3.4 (95% CI; 1.3–9.1) for the GSTP1–105Ile/Ile genotype (p = 0.01). Conclusions: The GSTP1-Ile105Val polymorphism is a strong predictor of clinical outcome for XELOXIRI therapy in mCRC pts. No significant financial relationships to disclose.
Thromboembolic events (TE) in men treated with bleomycine-etoposide-cisplatin (BEP): A monocentric review over one year.
Authors: Helen Jane Boyle, Emilie Lavergne, Nathalie Bonnin, Herve Rosay, Aude Flechon
Journal: Journal of Clinical Oncology (2014)

375 Background: BEP chemotherapy (CT) is the standard regimen for patients (pts) with metastatic germ cell tumours (MGCT). Over the past years, it seemed that more pts developed TE. Methods: Files of all male pts treated with BEP CT for a MGCT, at the Centre Léon Bérard in 2012, were reviewed. The incidence of thrombosis was assessed and then, the study population was described by comparing affected pts with the others using the non parametric Wilcoxon test for the quantitative data and Fisher exact test for the qualitative one. Results: Finally, 45 men received BEP for MGCT at our institution in 2012. Median age at CT initiation was 33.6 years (range: 16.9-43.6). All pts but 1 had a testicular primary, 1 had a mediastinal primary. Ten had seminomas (22%) and 35 a non-seminomatous tumour (78%). According to the IGCCCG classification, 28 pts were classified as good prognosis (62%), 12 as intermediate prognosis (27%) and 5 as poor prognosis (11%). Seven pts received CT on a port-a-cath (16%), 13 pts on a brachial PICC line (29%) and 25 on a central venous cathether (CVC) inserted in the jugular (55%). Fifteen pts (33%) developed venous thrombosis: 4 of them had a pulmonary embolism. The TE was symptomatic for 9 pts and was discovered on a routine CT-scan for the other 6 pts. TE was related to tumoral compression for 4 pts (27%, 3 TE diagnosed before CT) and to the venous catheter for 8 pts (53%). For the 3 other pts no “obvious” cause was found. Median time from catheter insertion to thrombosis was 35 days (range: -32-80 days). TE occurred in 29% of pts with a porthacath, 31% of pts with a PICC line and 36% of pts with a CVC. No significant relationship was observed between thrombosis occurrence and age, IGCCCG prognostic group, type of venous catheter, presence of metastasis and lymph nodes status. Among the 27 pts (60%) who underwent post-CT surgery, 41% were on curative anticoagulant therapy (low molecular weight heparin). Conclusions: Incidence of TE is higher in this small study than those reported in other series. The reason for this is unclear and needs more investigations. Prospective evaluation of prophylactic use of anticoagulants and/or of new practices concerning catheters, as removing it on day 6, to avoid TE may be explored.
Evaluation of physician knowledge and referral practices for colorectal cancer (CRC) genetic risk assessment: The experience at the Hospital of University of Pennsylvania (HUP).
Authors: J. Jenab-Wolcott, K. Tan, D. F. Heitjan, B. J. Giantonio, M. Garin, J. Powers, J. Stopfer, T. Hoops, A. Rustgi
Journal: Journal of Clinical Oncology (2011)

379 Background: 3-5% of CRCs are due to inherited genetic mutations. We surveyed knowledge and practices of academic physicians for identification and care of individuals at risk for inherited CRC. Methods: 264 physicians (oncologists (ON), gastroenterologists (GA), surgeons, internists, gynecologists, and radiation oncologists) at HUP were invited to participate in a web-based 9-min survey. The ability to obtain appropriate medical history and to make referral to genetic services was evaluated. Knowledge of hereditary CRC syndromes was examined both pre and post viewing of an educational web-page on inherited CRCs. Mantel-Haenszel, Fisher exact, and McNemar statistical tests were applied. Results: Response rate was 33.3%; and of those, 97.4% accessed the educational webpage. In the cohort, 98.9 % obtained a medical history very frequently (VF), 88.6% obtained cancer history in 1 st and 45.5% in the 2 nd degree relatives VF, and 63.9% asked about the relatives' age at time of cancer diagnosis VF. Of those most likely to care for patients with CRC, the GA more frequently asked about relatives' age at cancer diagnosis (p=0.014) and family history of polyps (p&lt; 0.001) than ON. GA were more likely than ON to refer patients for genetic counseling (73.9% vs. 36.8%, p=0.008). GA had superior knowledge of the availability of genetic testing for Lynch syndrome (LS) (95.6% GA vs. 63.2% ON, p=0.005) and for familial adenomatous polyposis (FAP) (100.0% GA vs. 65.8% ON, p&lt;0.001). For the entire cohort, the educational intervention raised awareness of genetic testing for LS (64.5% pre vs. 94.7% post, p&lt;0.001), FAP (69.7% pre vs. 97.4% post, p&lt;0.001), and Peutz-Jeghers Syndrome (31.6% pre vs. 84.2% post, p&lt;0.001); and it significantly improved recognition of LS family pedigrees and selection of appropriate surveillance. Conclusions: Of the respondents, GA are more likely to obtain a detailed family history, utilize genetic services, and have a greater awareness of the availability of genetic testing, than ON. A simple educational intervention improves physician knowledge on inherited CRC risk recognition and surveillance recommendations. No significant financial relationships to disclose.
Perception of helpfulness of a question prompt sheet among cancer patients attending outpatient palliative care.
Authors: Joseph Anthony Arthur, Sriram Yennu, Kresnier Perez Zapata, Hilda Cantu, Diane D Liu, Jimin Wu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

25 Background: Data on the use of question prompt sheets (QPS) in palliative care is limited. Our team previously developed a single page QPS using a Delphi process. The main objective of this study was to determine the perception of helpfulness of a QPS in patient-physician communication among advanced cancer outpatients. Methods: 104 eligible patients received the QPS for use during their first palliative care clinic. Patient and physician perceptions about the QPS were assessed at the end of the visit. Patients’ anxiety was also measured pre- and post-consultation using the Spielberger State Anxiety Inventory. Results: 100/104 (96%) patients completed the study. Among those responders, most agreed that the material was helpful in communicating with their doctor (77%), clear to understand (90%), had the right amount of information (87%), and they would use a similar material in the future (76%) and recommend it to other patients(70%). Overall, 92% were satisfied with their consultation visit. Physicians perceived that the QPS was helpful to 68% of the encounters and it did not prolong the consultation in 73% of the encounters. Physician agreement on helpfulness of the QPS was not significantly different from the patients (p = 0.3). Patient anxiety improved after consultation from a mean (SD) STAI score of 39.2 (12.8) to 33.8 (10.7), p ≤ 0.0001. Conclusions: The QPS was perceived as helpful in patient-physician communication among advanced cancer outpatients and it did not increase patient anxiety. Physicians similarly reported that the QPS was helpful and it did not prolong clinic visits. Further research is needed for its widespread adoption and integration into routine clinical practice.
Correlation of Clinical Response to Dasatinib (BMS-354825) with BCR-ABL Mutation Status in Imatinib- Resistant Patients (pts) with Chronic Myeloid Leukemia (CML) Treated at MD Anderson Cancer Center (MDACC).
Authors: Elias Jabbour, Jorge Cortes, Moshe Talpaz, Dan Jones, Susan O’Brien, Claude Nicaise, Hagop Kantarjian
Journal: Blood (2005)
Circumferential resection margin (CRM) in esophageal (OC) and gastroesophageal (GOJ) cancers.
Authors: D. B. Landau, C. G. Collins, E. Perry, Y. Suh, A. Grieves, B. Gill, A. Botha, R. Mason, A. Jacques
Journal: Journal of Clinical Oncology (2011)

69 Background: We hypothesized that CRM size affect survival and local recurrence for OC and GOJ cancer. We also assessed the utility of CT in predicting margin status. Methods: A retrospective analysis of a prospective database was carried out on all patients who had esophagectomy between January 2000 and July 2008. Patients diagnosed with OC and GOJ tumors on final pathologic examination were included. Distance from the CRM was assessed by a specialist upper GI pathologist. Two radiologists, blinded to postoperative margin status, reviewed preoperative CT scans using 16 separate parameters, comparing them to measured CRM status. Results: 419 patients were assessed. 223 pts had OC or GOJ type 1 tumors, average age 62 years (range 36–80), mean follow-up 5.8 years (2-9.5). There were 125 deaths and median overall survival (OS) 3.33 years (95% CI 2.76-6.24). 76 patients had recurrence at a median of 1.3 years (0.1-4.7). For 144 patients had OC or GOJ type 1 T3 tumors. Selected results are presented in the Table. There was no CRM size above which there was no further reduction in recurrence. Postoperative chemoradiation did not improve OS (p=0.79) or recurrence (p=0.96) in patients with CRM of 0-1 mm. In 50 patients the CT parameters significantly correlated with margin status were largest axial diameter (p=0.003) and contact with adjacent structures (p=0.005). A complete statistical review with multivariate and subgroup analyses will be presented. Conclusions: CRM size is strongly correlated with survival and recurrence in OC and type 1 GOJ tumors. Prediction of a close CRM could be used to select for more intensive therapy prior to undergoing radical surgery, such as chemoradiation. Preoperative CT can help in this prediction. [Table: see text] No significant financial relationships to disclose.
Outcomes by hypomagnesemia (hypomag) in the randomized phase III ASPECCT trial of patients (pts) with chemofractory wild-type (WT) <i>KRAS</i> exon 2 metastatic colorectal cancer (mCRC).
Authors: Marc Peeters, Tae Won Kim, Jin Li, Stefano Cascinu, Paul Ruff, Attili Venkatasatya Suresh, Anne Thomas, Sergei Tjulandin, Xuesong Guan, Tien Hoang, Yong Jiang Hei, Timothy Jay Price
Journal: Journal of Clinical Oncology (2016)

507 Background: ASPECCT demonstrated that panitumumab (pmab) was noninferior to cetuximab (cmab) for overall survival (OS). Ad hoc analyses from ASPECCT suggested that hypomag was associated with better outcomes for pmab and cmab (Price 2015). However, results from the phase 3 NCIC CTG/AGITG CO.17 trial indicated hypomag at day 28 was associated with worse outcomes for cmab (Vickers 2013). Methods: Patients (pts) with chemorefractory WT KRASexon 2 mCRC were randomized 1:1 to receive pmab or cmab. Ad hoc analyses by hypomag were performed from the final analysis of ASPECCT at week 5, consistent with the NCIC CTG/AGITG CO.17 trial analysis (Vickers, 2013). Results: 999 pts were treated: 496 received pmab and 503 received cmab. Any grade hypomag was 29.0% and grade ≥3 was 7.3% in the pmab arm vs 19.3% and 2.8% in the cmab arm, respectively. In the pmab arm, 1.2% of pts discontinued treatment and 5% of pts had dose modifications due to hypomag vs 0.4% and 3% in the cmab arm, respectively. Efficacy results by hypomag are shown (Table). Conclusions: In ASPECCT, rates of hypomag were higher in the pmab vs the cmab arm. Pts who developed any grade hypomag with pmab or cmab had longer median OS compared with those pts who did not. Consistent with previous analyses, development of hypomag at week 5 was associated with worse median OS for cmab. Clinical trial information: NCT01001377. [Table: see text]
The efficacy of prophylactic GCSF for FOLFIRINOX.
Authors: Tetsuji Terazawa, Masahiro Goto, Miyamoto Takahiro, Ken Asaishi, Fukutaro Shimamoto, Shin Kuwakado, Hitoshi Nishitani, Takayuki Kii, Kazuhide Higuchi
Journal: Journal of Clinical Oncology (2015)

274 Background: Granulocyte Colony-Stimulating Factors (GCSF) is used as supportive care in cancer management when patients (pts) receive chemotherapy with high risk of febrile neutropenia (FN). Peg-GCSF is unapproved in Japan at the time of Aug 2014. Hence, phase II study of combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) for Japanese pts with advanced pancreatic cancer showed FN; 22% and severe neutropenia; 77.8%. Purpose of this retrospective study was to describe the incidence of FN and severe neutropenia during the first cycle of FOLFIRINOX with prophylactic GCSF (pGSF). Methods: Between January 2014 and August 2014, the pts who received FOLFIRINOX with pGCSF were examined retrospectively. The adverse events and detail of pGCSF administration during first cycle were investigated. Results: Among five pts administered FOLFIRINOX, 4 pts received pGSF in first cycle. All patients received FOLFIRINOX without dose reduction. The patient characteristics were as follows: median age (range), 58 (50-66); male/ female, 3/1; PS 0/1, 1/3. The detail of UTG1A1 (*6/ *28) was as follows: (wild type/ wild type), 2pts; (wild/ hetero), 1pt; (hetero/ hetero), 1pt. Hematological adverse events (grade 1/2/3/4) were as follows: leukopenia (0/1/2/0), neutropenia (0/1/0/1), thrombocytopenia (0/4/0/0), FN (0/0/1/0). The patient who occurred grade4 neutropenia and grade3 febrile neutropenia had UTG1A1 *6 hetero/ *28 hetero. Non-hematological adverse events (grade 1/2/3/4) were as follows: elevated GOT (2/1/0/0), elevated GPT (2/1/0/0), elevated T-Bil (0/0/0/0), anorexia (1/2/1/0), fatigue (2/1/0/0), nausea (0/1/2/0), diarrhea (1/1/0/0). The median starting date of pGSF administration was 4.5 (3-7). The median number of pGSF administration was 7.5 (6-9). Conclusions: Although this was retrospective and small study, pGSF appeared to be effective for prevention of severe neutropenia and FN. Hence pGSF might increase dose intensity of FOLFIRINOX.
Survival as a measure of quality of cancer care and advances in therapy: Lessons learned from analyses of the National Cancer Data Base (NCDB).
Authors: Lawrence N. Shulman, Bryan E. Palis, Ryan M. McCabe, E. Greer Gay, Katherine Mallin, Ashley Loomis, David P Winchester, Daniel P. McKellar
Journal: Journal of Clinical Oncology (2016)

173 Background: Many quality metrics of cancer care are process measures, based on whether a patient received recommended treatment for diagnosis and stage of their disease. Survival is dependent on patient characteristics, disease specifics, and care received (surgery, systemic therapies, radiation). Some argue survival is the ultimate measure of cancer care quality. Survival calculated from registry data may be a better indication of the real effects of new therapies as it contains a broad representation of patients who may not meet the eligibility criteria for clinical trials. Methods: The NCDB is composed of registry data from approximately 1,500 hospital based cancer programs, and includes stage, demographic data, co-morbidities, treatments, and vital status. Survival analyses were derived from NCDB data for all stages of breast cancer, non-small cell lung cancer (NSCLC), and pancreatic cancer. These diseases were selected because breast cancer has a high survival rate, whereas NSCLC and pancreatic cancer are diseases with a poor prognosis, but recent advances may have improved survival. Un-adjusted and risk adjusted survival were analyzed by socioeconomic, tumor, and hospital factors including stage, comorbidities, diagnosis year (to assess new treatment trends), and type of institution (academic, comprehensive community, and community cancer programs). Results: Results for these diseases and variables noted will be presented. Whereas better un-adjusted survival rates were often seen at academic cancer programs, differences disappeared after risk-adjustment. Improved survival was seen in more recent years, probably representing new treatment effects, though gains were modest and stage dependent. Conclusions: Measuring survival across hospitals and regions is critical to understanding the state of cancer treatment nationally and the effect of quality and therapy advances on patients across a variety of clinical settings. Methodologic challenges in analyzing and interpreting survival data must be realized, and continued innovation in the collection and analysis of data is needed.
Association of human papillomavirus and squamous cell carcinoma of esophagus: A SEER database analysis.
Authors: S. Kato, M. Pu, W. L. Read
Journal: Journal of Clinical Oncology (2011)

e14634 Background: Squamous cell carcinoma (SCC) of the esophagus is generally associated with tobacco and alcohol use. However, there are multiple published reports suggesting a subset of SCC of esophagus is associated with human papillomavirus (HPV) infection. HPV is well known to be associated with SCC of the anus and tonsil. Patients with HPV-positive SCC do well with primary chemoradiation and it is possible subset of esophageal cancer might also do well with primary chemoradiation. Prior analyses of the Surveillance, Epidemiology, and End Results (SEER) database showed that the incidence of these HPV associated SCC in the younger population are increasing. We used the SEER database (1973-2007) to evaluate epidemiological similarities between HPV associated SCCs. Methods: We assessed the association of HPV and SCC of esophagus by evaluating epidemiological similarities between SCC of tonsil, anus, and esophagus among the younger age group (age 20 to 44) and older age group (age above 45) of patients. Patient characteristics, 5-year relative survival, and annual percentage changes (APC) in incidence rates were evaluated. Results: We identified 15,825 SCC of the tonsil, 25,943 SCC of the esophagus, and 9,437 anal SCC. Among the younger age group, a significant increase in the APC was seen in anal SCC (APC= +6.7; 95% CI [5.3,8.0]; p<0.05) and SCC of tonsil (APC= +3.5; 95% CI [2.5,4.5]; p<0.05), whereas the APC of SCC of esophagus in younger age group showed a significant decrease (APC= -2.0; 95% CI [-2.8, -1.1]; p<0.05) (Table). Conclusions: Despite multiple studies suggests SCC of esophagus is associated with HPV infection, the incidence of SCC of the esophagus has not changed in the same manner as SCCs that are strongly associated with HPV. This suggests that in the population studied, SCC of the esophagus may not be associated with HPV. Future work includes identifying subgroups of the patients whose SCC was probably associated with HPV by incorporating factors such as race or sex. Age 20-44 Age ≥ 45 5-year relative survival APC 95% CI 5-year relative survival APC 95% CI Anal SCC 67.2% 6.7* 5.3, 8.0 68.3% 3.5* 3.1, 3.9 Tonsil SCC 70.1% 3.5* 2.5, 4.5 54.1% 0.3* 0.1, 0.6 Esophageal SCC 18.6% -2* -2.8, -1.1 10.4% -2.4* -2.9, -2.0 * p<0.05
Individual attributions of living longer with HER2+ metastatic breast cancer: Findings from a community web-based survey.
Authors: Musa Mayer, Matthew Sussman, Anthony Masaquel, Tripthi Kamath, Catherine Lai, Debu Tripathy, Sara A. Hurvitz, Joseph Menzin
Journal: Journal of Clinical Oncology (2014)

197 Background: Advances in targeted therapy have led to an increase in the median overall survival in patients with HER2+ metastatic breast cancer (MBC). However, patient attributions related to living longer have not been studied. Methods: A one-time, web-based survey was administered through multiple US-based breast cancer organizations. The inclusion criteria were being female, age 18+, having HER2+ MBC, and living in the US. The surveys included health related quality of life (HRQL), symptom burden, activities of daily living, satisfaction with medical care, work productivity, and attributes of living longer. To assess beliefs about length of survival with HER2+ MBC, participants were asked to rate the importance of 16 items. Descriptive results were stratified by time since metastatic diagnosis and HRQL. Results: Of 560 attempted surveys, 365 (65%) participants met inclusion criteria. Mean (SD) age was 53.6 (10.5) years, 93% were white, and 27% reported having participated in a clinical trial. 59% of respondents reported living ≥4 years since HER2+ MBC diagnosis. Common reasons patients gave for living longer included: choosing the right doctor/medical team (91%), having a positive outlook on life (79%), and learning about the disease or treatments (79%). Women with &lt;4 years since HER2+ MBC diagnosis were more likely to report having a positive outlook on life (85% vs 76%), using complementary and alternative medicine (45% vs 36%) and exercising regularly (74% vs 66%) compared with those having ≥4 years since diagnosis. Women reporting a better compared with a poorer HRQL reported more frequent regular exercise (73% vs 49%) and more often had a positive outlook on life (86% vs 64%). Conclusions: To our knowledge, this is the first study of women with HER2+ MBC and their attributions about length of survival. Having the right medical team, remaining positive, and being educated about the disease and its treatments were most important to participants. Women reporting better quality of life were more likely to report multiple attributions of living longer. HRQL and patient perceptions about their survival are important factors that should be considered in providing patient-centered care.