tbuckley/cabot-search huggingface dataset:
A retrospective analysis of the demographic profile and clinical outcomes of stage III colon cancer patients treated with adjuvant chemotherapy in a real-world perspective.
Authors: Praveen Ramakrishnan Geethakumari, Sherry Pomerantz, John Charles Leighton
Journal: Journal of Clinical Oncology (2014)

648 Background: It is standard to use results of randomized controlled trials (RCT’s) for therapeutic decisions in community oncology. However participant selection in trial environments may not reflect real-world scenario. We aim to perform a retrospective analysis of patient profile and treatment outcomes in a community cancer center. Methods: Patients with stage III colon cancer offered adjuvant chemotherapy after curative resection from 2003-2010 (N=177) were reviewed. Eighty-seven patients with complete medical records were analyzed. Patient eligibility was assessed on criteria from the MOSAIC and NSABP C-07 trials. Eligible and ineligible patients were compared using Fisher’s exact test, Student’s t-test and Kaplan-Meier survival analysis. Results: The study group (females: 53%) with mean age of 65 years, was predominantly African American (60%). ECOG performance status was ≥ 2 in 13% patients. Only 29% satisfied all standard eligibility criteria. Ineligibility characteristics included age &gt; 75 years (21%), non-malignant severe systemic disease (10%) and &gt; 42 days from surgery to chemotherapy (39%). Seventy-five patients (86%) received chemotherapy. Chemotherapy regimens included FOLFOX (51%), FLOX (10%), FL (29%) and Capecitabine (8%). Total planned dose had to be modified in 64% patients with mean doses of 89% 5-fluorouracil and 79% oxaliplatin employed. The 3-year disease free survival (DFS) was 53% and 5-year overall survival (OS) was 56%. Age ≥ 69 years was significantly associated with poor 3-year DFS (P=0.013). On Kaplan-Meier survival analysis, the ineligible patient group had significantly reduced overall survival (hazard ratio, 2.88; 95% CI, 1.05-4.82; P= 0.037). Conclusions: This pilot venture studied adjuvant management of Stage III colon cancer in a real-world setting. Our results reveal that over 70% patients did not meet standard eligibility criteria and show decreased 5-year OS among these patients that needs to be addressed in future prospective RCT’s.
A Retrospective Comparison of Once-Daily Prolonged-Release Tacrolimus Versus Twice-Daily Tacrolimus in Allogeneic Bone Marrow Transplantation from Unrelated Donors
Authors: Shingo Yano, Takeshi Saito, Hiroki Yokoyama, Tomohito Machishimia, Takaki Shimada, Yuichi Yahagi, Shinobu Takahara, Yoji Ogasawara, Katsuki Sugiyama, Jiro Minami, Yutaro Kamiyama, Atsushi Katsube, Noriyuki Morikawa, Kazuhito Suzuki, Yumiko Inui, Noriko Usui, Keisuke Aiba
Journal: Blood (2014)
Genomic determinants of prognosis in esophageal adenocarcinoma: Using computational methods to account for gene-gene interactions.
Authors: Eric Morgen, Xiaowei Shen, Thomas L. Vaughan, David Whiteman, Anna H. Wu, Marilie D. Gammon, Wong Ho Chow, Daniel O. Stram, Yvonne Romero, Wei Xu, Geoffrey Liu
Journal: Journal of Clinical Oncology (2014)

42 Background: Methods of stratifying esophageal adenocarcinoma patients into prognostic groups are needed, as are new insights into genetic determinants of disease behaviour. Prognosis is likely to have non-negligible genetic influences, as mediated by host responses to tumor, resistance to therapeutic side-effects, and/or an influence on tumor development. Prior studies have used candidate-gene approaches. We took an alternative approach, using an unbiased, genome-wide approach, and novel analytic methods that may be better able to detect multi-gene interactions, which may contribute the majority of genetic effects for many clinical phenotypes. Methods: Germline DNA from a Toronto-based cohort of EAC patients (n=270) was analyzed by Omni1 Quad microarray as part of the BEAGESS initiative. Quality control and analysis was performed using PLINK, R, and GenABEL software packages. A Cox proportional hazards (CPH) model for progression-free survival tested each polymorphism for independent effects at a genome-wide significance level of P &lt; 1E-07, adjusting for population stratification. While classical analysis has limited ability to detect gene-gene interactions, a Random Survival Forest algorithm was used to detect effects based on the complex interactions among top 1,000 polymorphisms by p-value ranking. Results: After data cleaning and standard GWAS quality control procedures, there were 735,309 SNPs and 245 patients remaining for analysis. The CPH model, adjusted for population stratification, produced a satisfactory Q-Q plot, and showed one SNP (rs7844673, Chr 8) that was significant at p=7.8E-8. In addition, Random Forest based variable selection produced a set of 20 polymorphisms that (1) reproduced 86% of the predictive ability of the full 1000 variables, and (2) also included the #3 ranked polymorphism by CPH modeling (rs9290822, Chr 3) upstream of the IGF2BP2 gene. Conclusions: A genome-wide approach has discovered two previously undescribed SNPs with a potential influence on EAC prognosis via a combination of independent and interactive effects. Validation in an independent cohort is currently being pursued.
Use of online resources by patients with cancer: The Canadian experience.
Authors: Lawson Eng, Dan Pringle, Catherine Brown, Xiaowei Shen, Mary Mahler, Chongya Niu, Jodie Villeneuve, Rebecca Charow, Christine Lam, Ravi M. Shani, Shabbir M. H. Alibhai, Jennifer M. Jones, Wei Xu, Geoffrey Liu, Samir C. Grover
Journal: Journal of Clinical Oncology (2012)

318 Background: Canadians are among the highest users of the Internet. Online health information resources are easily accessible and provide quick information, but concerns exist about their role within a physician–patient relationship. Methods: Cancer patients across multiple disease sites, recruited from a regional cancer center, were interviewed regarding their internet use for health-related data. Descriptive statistics characterized online resource usage. Univariate and multivariate logistic regression models evaluated the association between socio-demographics, functional status, clinico-pathological variables and internet usage. Results: Of 191 patients in an interim analysis, 87% had home internet access. Google was the most commonly accessed website (79%), followed by cancer society websites (43%), Mayo Clinic (32%) and Wikipedia (28%). Disease-specific information (91%) was more commonly researched than information about specific physicians (30%). As expected, being married, having completed high school, earning a higher income and having home internet access were each associated with accessing information online (p&lt;0.05). Patients were more likely to access disease-specific information through eMedicine than Wikipedia. Younger patients were more likely to evaluate support group information (aOR=5.9, 95%CI [1.6-21.3], p=0.02) and cancer society websites (aOR=2.6 [1.2-5.4], p=0.04). More educated patients used cancer society (aOR=2.7 [1.3-6.0], p=0.03) and subscription websites (aOR=3.8 [1.6-8.8], p=0.01). Surgical patients used subscription websites more than non-surgical patients (aOR=3.9 [1.7-8.8], p=0.006), obtaining disease-specific information (aOR=5.0 [1.4-18.5], p=0.04). Conclusions: Cancer patients commonly acquire health information from search engine queries. Socio-demographic and clinico-pathological variables affect online information access among cancer patients. Oncologists need to consider the potential benefits and pitfalls of patient online use in cancer management and in their physician-patient communication and shared decision making. Recruitment ends in August 2012 and data on the full 400 patient cohort will be presented. GL and SCG are co-senior authors.
Efficacy and safety result of trastuzumab (T-mab) and paclitaxel for T-mab naive patients with HER2-positive previously treated advanced or recurrent gastric cancer (JFMC45-1102): Final report.
Authors: Tsunehiro Takahashi, Kazuhiro Nishikawa, Akira Miki, Hirokazu Noshiro, Takaki Yoshikawa, Yasunori Nishida, Satoru Iwasa, Hiroto Miwa, Toshiki Masuishi, Kazuhiro Yoshida, Yasuhiro Kodera, Narikazu Boku, Yasuhide Yamada, Satoshi Morita, Mitsuru Sasako, Yoshihiko Maehara, Masaki Kitajima, Junichi Sakamoto, Shigetoyo Saji, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2014)

79 Background: The global, randomized, phase III ToGA study showed that the first-line treatment of trastuzumab (T-mab) combined with capecitabine and cisplatin a survival (OS) benefit for patients (pts) with HER2 positive advanced or recurrent gastric cancer. However, there is no report concerning about the efficacy and safety of T-mab containing second-line treatment for T-mab naïve pts with HER2 positive advanced or recurrent gastric cancer. Therefore, we planned a phase II study of paclitaxel plus T-mab in this setting. Methods: JFMC45-1102 is multicentre phase II study. Pts with HER2 positive (IHC3+ or IHC2+/FISH+), histologically confirmed gastric adenocarcinoma, age ≥ 20, received one or more prior chemotherapy but no prior therapy with T-mab, normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Pts received paclitaxel (80 mg/m 2 on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg for the initial dose, followed by 6 mg/kg q3w) until disease progression, unacceptable toxicity or patient’s refusal. The primary endpoint was overall response rate (ORR), and the secondary endpoints include progression free survival (PFS), time to treatment failure (TTF), OS and safety. Results: A total of 47 pts were enrolled from September 2011 to March 2012.The primary endpoint ORR was 37.0% (95%CI, 23 to 52).Complete response was observed in 1 case (2.2%).The PFS data was matured, and the median PFS was 5.09 months (95%CI, 3.79 to 6.49), TTF 5.09 months (95%CI, 3.72 to 6.49), OS 16.81 months (95%CI, 13.54 to 18.65). One patient died of lung pulmonary fibrosis during therapy. The most common grade 3-4 adverse events were leucopenia (17.4%), neutropenia (32.6%), anemia (15.2%). Conclusions: Combination chemotherapy of paclitaxel plus T-mab is generally well tolerated and showed promising activity for T-mab naïve patients with HER2 positive previously treated advanced or recurrent gastric cancer. Clinical trial information: UMIN000006223.
Prognostic role of <i>PI3KCA</i> and <i>TP53</i> in HPV-negative oropharyngeal cancers (OPCs).
Authors: P. Bossi, F. Perrone, R. Miceli, L. Locati, C. Bergamini, A. Mirabile, R. Granata, C. Resteghini, B. Cortelazzi, M. Orsenigo, C. Fallai, E. Orlandi, S. Pilotti, L. F. Licitra
Journal: Journal of Clinical Oncology (2011)

5573 Background: HPV-negative OPCs have a worse outcome as compared to HPV positive. Some molecular alterations (TP53 mutations and inverse correlation with EGFR deregulation) have been typically associated with HPV negativity, without prognostic relevance. Among HPV negative OPCs, markers of resistance to EGFRpathway inhibition need to be better defined. Methods: We retrospectively examined 73 consecutive HPV-negative OPC patients (pts) primarily treated between 1/1992 and 12/2000 with surgery, followed by postoperative radiation (PORT) in case of high risk pathologic exam. FISH analysis of EGFR, IGF1R and PI3KCA were conducted on 69, 60 and 63 available formalin fixed paraffin embedded tumor samples. TP53 was classified in 67 pts according to functional properties of the protein by Kato. We studied the association between EGFR, IGF1R, PI3KCA, TP53and disease-free survival (DFS) by univariable (Kaplan-Meier curves) and multivariable analyses (Cox models including TP53, RT administration and stage). Results: The great majority of the pts had stage III-IV (92%) and 64% was treated also with PORT. In univariable analysis PI3KCA amplification and polisomy were associated with better prognosis, confirmed by multivariable analysis (HR: 3.20, p=0.003). No significant association with stage and PORT was identified. Combined Kaplan-Meier curves of PI3KCA and TP53 showed a TP53-independent DFS in the group with amplification/polisomy and a significant worse prognosis with not functional vs functional TP53 in the group with disomy of PI3KCA (p=0.002). Conclusions: In our primarily surgical treated series of HPV-negative OPCs, an increased PI3KCA copy number occurred in 40% of the cases and it helped to identify a subgroup of pts with better prognosis. Presence of not functional TP53 mutations had a negative impact on the prognosis of pts without alterations of PI3KCA. Molecular marker Gene status Number of pt (%) Kaplan-Meier 5-year DFS Log-rank test p EGFR Amplification 5 (7%) 42% 0.431 Polisomy 25 (36%) Disomy 39 (57%) 31% IGF1R Amplification 3 (5%) 39% 0.123 Polisomy 13 (22%) Disomy 44 (73%) 32% PI3KCA Amplification 7 (11%) 46% 0.028 Polisomy 18 (29%) Disomy 38 (60%) 24% TP53 Functional 44 (66%) 39% 0.302 Not functional 23 (34%) 29%
“Stop smoking!”: Do we say it enough?
Authors: Jessica Ann Reifer Hildebrand, Sangeeta Sastry, Ashley Adams
Journal: Journal of Clinical Oncology (2013)

e17500 Background: There are clear benefits of smoking cessation after the diagnosis of Bronchogenic Carcinoma (BC). Patients who quit smoking after the diagnosis of BC report lower levels of pain and are less likely to develop a second primary tumor when compared to patients who continue to smoke after they are diagnosed. Persistent smoking is also associated with poor performance status and survival outcomes. Evidence suggests that smokers are more likely to quit if they are counseled by their physicians. Yet, there may be a prevailing belief among physicians that treating tobacco dependence is futile in this population. The purpose of this study was to investigate whether physicians addressed smoking cessation with patients who were diagnosed with BC. Methods: A retrospective chart review of patients who were diagnosed with BC was conducted at a community medical center between 2008 and 2010, using the hospital’s cancer registry. Demographic information including age, race, sex, AJCC stage, and smoking status at the time of diagnosis was collected. Evidence of tobacco cessation counseling was sought through billing codes, physician notes, and orders surrounding the time of diagnosis. Results: A total of 948 patients were diagnosed with lung cancer between 2008 and 2010. 438 were current smokers at diagnosis, 422 were former smokers, and 88 had never smoked. Of the 438 smokers, only 36% were counseled on smoking cessation. On average, each patient encountered 3 different physicians in both the inpatient and outpatient settings. Of note, Stage I patients were 1.7 times more likely to be counseled than those with Stage IV disease (p=0.017). There was no significant difference between the counseled group and the non counseled group in regards to age, race, or sex. Conclusions: In spite of evidence that smoking cessation is beneficial even after the diagnosis of BC, physicians are not counseling their patients sufficiently. Reasons physicians may fail to counsel include: an inability to effectively assess tobacco dependence, competing concerns during patient encounters, and reduced awareness of current quality measures. With the implementation of quality improvement programs, we suspect that smoking cessation counseling for patients with BC will improve in the community setting.
The effect of dual PI3K/mTOR inhibitor NVP-BGT226 on cell cycle and survivin and STAT3 gene expression in human pancreatic cancer cell lines.
Authors: W. Glienke
Journal: Journal of Clinical Oncology (2011)

e14523 Background: The phosphatidylinositol-3-kinase (PI3K) pathway is one of the most commonly activated signaling pathways in pancreatic cancer. The inhibition of this transducing pathway may open new options for the treatment of pancreatic cancer. NVP-BGT226 is a novel dual class PI3K/mammalian target of rapamycin (mTOR) inhibitor that has entered Phase I/II clinical trials. Methods: We have tested the effects of NVP-BGT226 on cell viability (M'TT assay), apoptosis (AnnexinV/PI-FACS and PARP1 cleavage), cell cycle (FACS PI/RNAse-staining) and expression of Survivin, STAT3 and BCL-xL with Real-time RT-PCR and Western blot in the human pancreatic cancer cell lines Panc-1, BxPc-3, AsPC-1 and MiaPaCa-2. Results: The cell viability decreased within 24-72 hours exposure to about 50% compared to untreated control cells in a concentration and but not time dependent manner. Apoptosis was not detected, but cell cycle analysis revealed that NVP-BGT226 induced predominantly a G0/G1-arrest to about 90-95%. Analysis with Real-time RT-PCR and Western blot showed a remarkable reduction of Survivin and STAT3 expression but an increase of the anti-apoptotic BCL-xL gene expression. Conclusions: The PI3K/mTOR inhibitor NVP-BGT226 induces G0/G1-arrest and and acts via downregulation of Survivin and STAT3.
The Choosing Wisely Canada cancer initiative.
Authors: Gunita Mitera, Andrea Bezjak, Christopher M. Booth, Guila Delouya, Christine Desbiens, Craig Earle, Kara E. Laing, Steven Latosinsky, Natasha Camuso, Mary Agent-Katwala, Geoff Porter
Journal: Journal of Clinical Oncology (2014)

5 Background: Choosing Wisely Canada is a campaign modelled after Choosing Wisely in the USA and aims, through a pan-Canadian cancer physician-based consensus process, to identify a list of low value or harmful cancer services/practices frequently used in Canada. The following describes the approach taken for this work related to cancer in Canada. Methods: A Task Force approach was used, facilitated by the Canadian Partnership Against Cancer (CPAC), and included representation from the Canadian Society of Surgical Oncology, Canadian Association of Medical Oncologists, and Canadian Association of Radiation Oncology, and an expert advisor. The methodology included four phases: (1) identify potentially relevant items and a framework for their subsequent selection; (2) develop a long list; (3) refine and reduce the long list to a short list; and (4) select and endorse a final list of low value or harmful cancer practices. Phases 2–4 followed a framework-driven consensus process and used a series of electronic surveys and voting processes. Results: For Phase 1, 66 cancer relevant practices were initially identified. The framework for subsequent selection included: (1) the size of population to which the practice is relevant; (2) frequency of use in Canada; (3) cost; (4) evidence of low value/harm; and (5) potential for change in use of the practice. The long list (41 practices) was refined and reduced to a short list of 19 practices and a final list including 10 practices. Of these, 5 are completely new, and 3 are revisions/adaptations practices from USA Choosing Wisely. Of the 10 practices, 6 are involve multiple disease sites, while 4 practices are disease-site specific. One practice relates to diagnosis, 6 are treatment- focussed, 2 target surveillance/survivorship, while one practice spans the cancer continuum from diagnosis through survivorship. Conclusions: Through CPAC facilitation, the collective input and work of three professional oncology societies informed this initiative. The content of the final list will be officially released through Choosing Wisely Canada in October 2014, and will be fully revealed at the ASCO Quality Care Symposium.
Investigation of the Role of Copy Number Variation In the Pathogenesis of Type 1 Von Willebrand Disease
Authors: Daniel J. Hampshire, Lisa D. Bloomer, Ahlam M. Al-Buhairan, Rachael E. Coyle, Raymon N. C. P. Vijzelaar, David Lillicrap, Paula D. James, Jeroen C. J. Eikenboom, Reinhard Schneppenheim, Francesco Rodeghiero, Robert R. Montgomery, Ian R. Peake, Anne C. Goodeve
Journal: Blood (2010)
Adjuvant chemoradiation to improve survival compared to adjuvant chemotherapy in selected patients with pancreatic cancer.
Authors: Aryavarta M. S. Kumar, Gavin Falk, Kevin L. Stephans, Matthew Walsh, Robert James Pelley, May Abdel-Wahab
Journal: Journal of Clinical Oncology (2014)

330 Background: While surgery remains the only potential curative option for resectable pancreatic cancer, adjuvant therapy improves outcomes over surgery alone; however, adjuvant recommendations of chemotherapy vs chemoradiation remain controversial. We present outcomes comparing the two adjuvant treatments. Methods: In our single institution review, 343 patients (2000-2012) had pancreatoduodenectomy for pancreatic cancer. Medical oncology made adjuvant recommendations. Chemotherapy was gemcitabine or 5-FU and radiotherapy prescription was 45-54 Gy. Locoregional recurrences (LRR) were operative bed or regional nodal failures. Results: Median follow up and median survival (MS) for all patients was 17.5 and 19.5 mo respectively. 130 patients had resection alone (A), 84 had adjuvant chemotherapy (B), and 129 had adjuvant chemoradiation (C). MS for groups A, B, and C were 13, 23 and 26 mo respectively. Locoregional recurrence (LRR) was 60%, 63%, and 38% and distant failure was 64%, 65%, and 66% for groups A, B, and C respectively. Group C had significantly lower LRR compared to group B (p=0.01) however, survival between groups B and C was not statistically significant (p=0.23). Angiolymphatic invasion (ALI) and perineural invasion were correlated with LRR (p&lt;0.01). Multivariable analysis showed LRR, laparoscopy, ALI, and the interaction term of LRR with surgical margin were significant predictors of survival (p&lt;0.05). MS of patients with lymph node ratio (LNR) &gt; 0.2 and LNR ≤ 0.2 was 18 and 27 mo respectively. Subgroup analysis showed survival advantages to adjuvant chemoradiation compared with adjuvant chemotherapy. R1 resections in groups B and C were 37% and 39% (p=ns) with MS of 16 vs 27 mo respectively (p=0.01). For patients with ≥ 8 LN dissected and LNR ≤ 0.2, MS was 24 vs 32 mo for groups B and C respectively (p=0.04). Conclusions: Adjuvant chemoradiation significantly decreases LRR in resected pancreatic cancer patients. Compared to adjuvant chemotherapy alone, adjuvant chemoradiation improved survival for patients with a 1) positive surgical margin and/or 2) LNR ≤ 0.2 with ≥ 8 LNs dissected.