tbuckley/cabot-search huggingface dataset:
Prognostic value of epidermal growth factor receptor gene amplification in surgically resected non-adenocarcinoma lung cancer patients.
Authors: Yaewon Yang, Hyun Chang, Jong-Seok Lee, YuJung Kim, Sang-hoon Jheon, Jin-haeng Chung
Journal: Journal of Clinical Oncology (2013)

e18553 Background: The purpose of this study is to investigate the prognostic role of genomoic gain and expression for epidermal growth factor receptor (EGFR) gene in surgically resected non-adenocarcinoma of non-small-cell lung cancer (NA-NSCLC). Methods: This retrospective study included 115 NA-NSCLC consecutive patients with available tumor tissue and survival data, median follow up period of 6.4 years. EGFR gene copy number and protein expression was evaluated using by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) in tissue microarray sections, respectively. Results: Among 115 patients, 99 patients (86.1 %) were with squamous cell carcinoma histology. EGFR gene amplification and high polysomy (EGFR FISH + ) were observed in 57 (49.6%) and 45 (39.1%) patients, respectively. Patients with EGFR FISH + had significantly shorter overall survival [median, 41 months vs. not reached (&gt;70 months), P = 0.011]. Multivariable model confirmed that patients with EGFR FISH + had a significantly greater risk of death than those with EGFR FISH-negative after adjusting pathologic staging, presence of pleural invasion, venous invasion and adjuvant chemotherapy (hazard ratio = 2.11, 95% confidence interval 1.23-3.61, P = 0.006). EGFR IHC expression did not associate with overall survival in same group. Conclusions: EGFR increased gene copy number is an independent negative prognostic factor in surgically resected NA-NSCLC.
U.S. Preventive Services Task Force (USPSTF) recommendations on breast cancer screening (BCS): Are they justified?
Authors: Lori H. Pai, Gary M. Strauss
Journal: Journal of Clinical Oncology (2013)

1584 Background: Nine randomized population trials (RPTs) on BCS with mammography have been reported. Conclusions based upon mortality (MOR) comparisons in RPTs have long led to uncertainty about whether BCS saves lives, especially in women in their 40s. In Nov 2009, USPSTF recommended against BCS in women 40-49 and biennial BCS for women &gt;50. By 2010, BCS fell by &gt;4% in US. Does the evidence support USPSTF recommendations? Methods: MOR quantifies the effect of intervention across an entire population. However, the key issue is whether BCS reduces MOR among those with disease. This is reflected by survival (SUR), not MOR. While SUR is considered flawed due to conventional screening biases, the confounding influence of these biases is misunderstood. In a RPT, randomization provides an opportunity to eliminate these biases, so that (SUR) may accurately reflect screening efficacy. MOR would be biased if randomization fails to produce populations at equal risk for the target disease. Results: Among 9 RPTs, significant MOR reductions were reported only in Swedish Two-County Study in women &gt;50 and in the Gothenburg Study in women 39-49. However, problems with randomization were responsible for MOR overestimating BCS efficacy in these trials. In 7 RPTs, significant MOR reductions were not seen. However, MOR underestimated BCS efficacy in several RPTs. The Canadian National BCS Study, the most influential RPT in women &lt;50 yrs, showed a trend toward increased BC MOR in the screened group. However, randomization failure was likely responsible for significantly more high risk BC in the screening group, which confounded MOR comparisons. Conclusions: It’s never been possible to justify BCS based on MOR comparisons in RPTs. While meta-analyses have been widely utilized, they can be biased when MOR fails to accurately reflect BCS in individual RPTs. Abundant evidence from RPTs supports that BCS leads to significant stage and SUR advantages not attributable to conventional biases, and which more accurately reflect BCS efficacy. The magnitude of benefit is similar for women in their 40s and for those &gt;50. USPSTF recommendations are not supported by the data. If fully implemented, these guidelines can lead to increased BC MOR in US.
Clinicopathological associations and prognostic implications of KRAS mutation in metastatic colorectal cancer (CRC) population over 9 years at a single institute.
Authors: Shruthi Melinamani, Lela Buckingham, Marisa E. Hill, William T. Leslie
Journal: Journal of Clinical Oncology (2017)

573 Background: Mutations in Kirstin RAS (KRAS) oncogene play a significant role in the constitutive activation of RAS/RAF/MEK/ERK pathway in CRC. Our objective was to evaluate the association of KRAS mutation status with the clinicopathological characteristics of the tumor and analyze prognostic implications of KRAS mutation in CRC patients. Methods: A total of 154 CRC patients diagnosed between 2007 and 2016 were included in this study. Formalin-fixed paraffin-embedded tissue from CRC patients who had metastatic disease were analyzed for KRAS mutations by allele-specific PCR. Baseline clinicopathological features and survival times were retrieved from electronic medical records. χ 2 , Fisher’s exact tests and Pearson’s correlation were used for association and binomial logistic regression to calculate the odds ratio. Kaplan Meier analysis and log rank test were used to compare survival outcomes. Results: KRAS mutations were identified in 61(39.6%) patients, 29(47.5%) were Caucasians, 22(36.1%) African Americans, 5(8.2%) Asians &amp; 5(8.2%) other ethnic groups. The median age was 65 years with 31(44.9%) male and 30(35.3%) female patients. The majority of KRAS mutations were G12D (27 cases, 44.26%) and G12V (17 cases, 27.86%). KRAS mutations were most frequent in CRC adenocarcinomas (50 cases, 86.2%; P = 0.011) with poorly differentiated histology (p &lt; 0.001) and current/former smokers (60.7% vs. 41.4%; P = 0.03). Advancing age (OR = 1.150; 95% CI = 1.049 to 1.261; P = 0.003), increasing body weight (OR = 1.799; 95% CI = 1.118 to 1.954; P = 0.034) and increasing BMI (OR = 1.131; 95% CI = 1.05 to 1.204; P = 0.002) were associated with increasing likelihood of KRAS mutation. Patients with KRAS mutation had a tendency to shorter median overall survival than those with wild-type KRAS (30.9 vs. 33.1 months; P = 0.951). Subgroup analysis demonstrated that the patients with KRAS mutations showed worse survival in the group with poorly differentiated histology (median, 5.7 vs. 21.6 months; P = 0.04). Conclusions: CRC patients harboring KRAS mutation constitute a heterogeneous group with distinct tumor characteristics and clinicopathological associations.
Retrospective safety assessment of bendamustine in patients with renal impairment.
Authors: Beth L Nordstrom, Kevin B. Knopf, Dana Teltsch, Robert Engle, Hooman Beygi, James A. Sterchele
Journal: Journal of Clinical Oncology (2012)

e13081 Background: Patients with non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are at risk for renal impairment as the median age at diagnosis is &gt;65 years. Bendamustine is a bifunctional alkylating agent with efficacy via several pathways and a manageable toxicity profile in NHL and CLL. There has been no published research on its safety in renally impaired NHL and CLL patients. Methods: In this retrospective study of 2 electronic medical record databases from US outpatient oncology practices, patients with NHL and CLL who had received ≥1 dose of bendamustine alone or with rituximab were identified and divided into investigator-defined subgroups: nonrenally impaired (creatinine clearance [CrCL] ≥40 or ≥60 mL/min) and renally impaired (CrCL &lt;40 mL/min). Patients who received drugs with &gt;5% risk of causing renal damage (eg, cisplatin, cyclosporine) were excluded. The study’s primary aim was to evaluate laboratory toxicities in the NHL and CLL groups. Results: Of 379 CLL patients, 42 had CrCL &lt;40, 144 had CrCL ≥40-60, and 193 CrCL ≥60 mL/min; of 561 NHL patients, 62 had CrCL &lt;40, 153 had CrCL ≥40-60, and 346 had CrCL ≥60 mL/min. Baseline characteristics were similar, except for more advanced age, shorter mean disease duration, and a slightly lower initial bendamustine dose in renally impaired patients. Mean total bendamustine exposure was 12 weeks for renally impaired vs 15 weeks for nonrenally impaired CLL patients, and ~16 weeks for both NHL groups. No statistically significant differences in laboratory toxicities were seen among the CLL groups, but renally impaired NHL patients had an increased risk for grade 3/4 thrombocytopenia (Cox hazard ratio [HR]: 2.57; 95% CI: 1.13, 5.85) vs those with CrCL ≥60 mL/min. In combined CLL and NHL groups, only grade 3/4 BUN increase was significantly higher for renally impaired patients vs those with CrCL ≥40 mL/min (HR: 2.36; 95% CI: 1.15, 4.86) or ≥60 mL/min (HR: 4.46; 95% CI: 1.79, 11.14). Conclusions: Though sample size and time of exposure limit the power of this study, the results support the safety of bendamustine in renally impaired NHL and CLL patients. Monitoring blood counts and renal function is probably prudent. Support: Teva Pharmaceutical Industries Ltd., Frazer, PA.
Phase I/II study of dianhydrogalactitol in patients with recurrent malignant glioma.
Authors: Kent C. Shih, Manish R. Patel, Nicholas A. Butowski, Jeffrey A. Bacha, Dennis Brown, Anne Steino, Richard Stephen Schwartz, Sarath Kanekal, Lorena Lopez, Suzanne Fields Jones, Howard A. Burris
Journal: Journal of Clinical Oncology (2015)

2023 Background: Glioblastoma multiforme (GBM) is the most common brain cancer. Front-line systemic therapy with temozolomide is often ineffective due to O6-methylguanine-DNA-methyltransferase (MGMT)-mediated resistance. Dianhydrogalactitol (VAL-083) is a bi-functional DNA alkylating agent that crosses the blood-brain barrier and overcomes resistance to MGMT in vitro. The goal of this clinical trial is to determine an appropriate dose for phase III trials in refractory GBM. Methods: Open-label, single-arm phase I/II dose-escalation study in patients with histologically-confirmed GBM, previously treated with radiation and must have failed both bevacizumab and temozolomide, unless contraindicated. The study utilizes a 3+3 dose-escalation design. Patients receive VAL-083 IV on days 1, 2, and 3 of a 21-day cycle. Tumor response is assessed according to RANO criteria prior to every other 21-day treatment cycle. Results: 25 patients have been enrolled across 8 dose cohorts ranging from 1.5 to 50mg/m2/d. A dose limiting toxicity consisting of grade 4 thrombocytopenia was observed at dose level 8 (50mg/m2/d). The DLT-related symptoms resolved rapidly and spontaneously without concomitant treatment. Prior to this, other treatment related toxicities have been mild to moderate and included two grade 1 lymphopenias and one grade 1 thrombocytopenia. Maximum tolerated dose (MTD) will be determined based on 3+3 design. Three patients had a response (stable disease or partial response) reporting improved clinical signs (maximum response of 84 wks). Pharmacokinetic analyses show dose-dependent linear systemic exposure with a short plasma 1-2h terminal half-life; Cmax ranged from 1130–739 ng/mL (7.7–5.1µM) at 40mg/m2/d. Compared to historical trials, the present regimen delivers substantively more drug by Cmax and dose intensity. A dose intensity of 25 mg/m2/wk in combination with radiation was previously shown superior to radiation alone against GBM; a dose intensity of 50 mg/m2/wk is achieved in the current trial. Conclusions: VAL-083 dosing may be limited by myelosuppression. The MTD will be studied in a Phase II expansion and possible phase III registration trial. Clinical trial information: NCT01478178.
HER2 expression and response to neoadjuvant chemoradiotherapy in esophagogastric adenocarcinoma.
Authors: Lizette Vila Duckworth, Ellie Chan, Ahmad Alkhasawneh, Tania Zuluaga-Toro, Xiaomin Lu, Steven J. Hughes, Thomas J. George
Journal: Journal of Clinical Oncology (2013)

e15145 Background: Targeting HER2 overexpression with trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival with clinical trials currently examining the impact of HER2 inhibition in early stage disease. This study analyzed the pattern of HER2 overexpression in matched-pair tumor samples of patients (pts) undergoing neoadjuvant chemoradiotherapy (chemoRT). Methods: This analysis included pts with EGA who underwent neoadjuvant chemoRT followed by esophagectomy at the University of Florida from 2001 to 2011 who did not receive anti-HER2 therapy. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded IHC was performed on paraffin embedded tumor specimens with HER2 expression scored as negative (-) (0, 1+), indeterminate (2+) or positive (+) (3+). Descriptive statistics, Chi-square exact test, uni and multivariate analyses were used for statistical analyses. Results: 49 pts (41M/8F) were analyzed with median age 65 years (39-87). Most tumors were stage II (55%) or III (43%). 9/49 pts (18%) had pathologic complete response (pCR), another 10/49 had near pCR or not enough tumor (NET) to examine. HER2 expression was more common in lower stages (stage I, II vs III). Baseline HER2 expression did not correlate with treatment response. Univariate analysis did not show significant correlation of age, stage, smoking, pre or post treatment HER2 expression with survival. For matched-pair samples failing to achieve pCR or NET (n=30), pre and post treatment HER2 expression profiles are presented in the Table. HER2 expression appears UP regulated in response to neoadjuvant chemoRT. Conclusions: Our study demonstrated the degree of pre-treatment HER2 expression in EGA does not predict the response to chemoRT. However, HER2 overexpression is more frequent in post treatment samples without pCR. This suggests that HER2 may be upregulated by chemoRT with unreliable concordance between pre and post treatment samples. This has implications for both early and advanced stage therapeutic interventions with targeted therapies. [Table: see text]
Effect of metformin on recurrence-free survival and overall survival in diabetic patients affected by advanced ovarian cancer.
Authors: Cecilia Simonelli, Monica Bertolotti, Paul Sabbatini, Jonathan S. Berek, Jacobus Pfisterer, Monica Binaschi, Isabella Otranto, Carlo Alberto Maggi, Simona Scartoni, Angela Capriati
Journal: Journal of Clinical Oncology (2013)

5522^ Background: Metformin, has recently shown some anti-cancer activities in ovarian cancer, both in vitro and in vivo. Methods: Analysis of Recurrence Free Survival (RFS) and Overall Survival (OS) was performed in patients (pts) with diabetes (D) treated with metformin (DMet + ) or not (DMet - ) enrolled in the MIMOSA trial, a randomized double-blind placebo-controlled international trial of Abagovomab maintenance therapy in 888 pts with advanced ovarian cancer. In the MIMOSA trial, no differences in the RFS and OS were observed between Abagovomab (n = 593) and Placebo arm (n = 295); hence, the present RFS and OS analysis (DMet + vs DMet - ) was run regardless of treatment allocation. A Cox proportional hazards model was used for adjusting the analysis for the predefined prognostic factors: Figo stage (III, IV), tumor size after debulking (residual tumor &lt;1 cm, &gt;1cm); CA125 serum level after 3 th cycle (&lt;35U/ml, &gt;35U/ml). In addition, comparison of RFS and OS was done between DMet + and the overall MIMOSA population not exposed to metformin (ALLMet - ), and between the overall diabetic pts (ALLD + ) and non-diabetic pts (ALLD - ). Results: In the ALL population (n = 888), 42 pts were affected by diabetes (ALLD + ) divided to DMet + (n = 27) and DMet - (n = 15), without difference in the prognostic factors distribution. When analysis was done in ALLD + , RFS median time was not reached in the DMet + group whereas it was 328 days [CI: 30-660] in DMet - group with HR favoring DMet + =0.419 [CI:0.175-1.002]; p = 0.05. Median OS time was also not reached in the DMet + group whereas it was 786 days [CI:262-NE] in DMet - group with HR=0.295 [CI:0.109-0.803]; p = 0.02. Interestingly HR for RFS time was still in favour of DMet + group when compared to the ALLMet - (n=861) with HR=0.575 (CI=0.324-1.022); p = 0.06. When ALLD + were compared with ALLD - (n = 846), no significant differences was detected in RFS and OS time. Conclusions: The present results are the first prospectively analyzed data demonstrating a favourable impact of metformin treatment on RFS and OS in pts affected by advanced ovarian cancer. Clinical trial information: NCT00418574.
Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications
Authors: Alcino Costa Leme, Ludhmila Abrahao Hajjar, Marcia S. Volpe, Julia Tizue Fukushima, Roberta Ribeiro De Santis Santiago, Eduardo A. Osawa, Juliano Pinheiro de Almeida, Aline Muller Gerent, Rafael Alves Franco, Maria Ignez Zanetti Feltrim, Emília Nozawa, Vera Regina de Moraes Coimbra, Rafael de Moraes Ianotti, Clarice Shiguemi Hashizume, Roberto Kalil Filho, Jose Otavio Costa Auler, Fabio Biscegli Jatene, Filomena Regina Barbosa Gomes Galas, Marcelo Britto Passos Amato
Journal: JAMA (2017)

Perioperative lung-protective ventilation has been recommended to reduce pulmonary complications after cardiac surgery. The protective role of a small tidal volume (VT) has been established, whereas the added protection afforded by alveolar recruiting strategies remains controversial.To determine whether an intensive alveolar recruitment strategy could reduce postoperative pulmonary complications, when added to a protective ventilation with small VT.Randomized clinical trial of patients with hypoxemia after cardiac surgery at a single ICU in Brazil (December 2011-2014).Intensive recruitment strategy (n=157) or moderate recruitment strategy (n=163) plus protective ventilation with small VT.Severity of postoperative pulmonary complications computed until hospital discharge, analyzed with a common odds ratio (OR) to detect ordinal shift in distribution of pulmonary complication severity score (0-to-5 scale, 0, no complications; 5, death). Prespecified secondary outcomes were length of stay in the ICU and hospital, incidence of barotrauma, and hospital mortality.All 320 patients (median age, 62 years; IQR, 56-69 years; 125 women [39%]) completed the trial. The intensive recruitment strategy group had a mean 1.8 (95% CI, 1.7 to 2.0) and a median 1.7 (IQR, 1.0-2.0) pulmonary complications score vs 2.1 (95% CI, 2.0-2.3) and 2.0 (IQR, 1.5-3.0) for the moderate strategy group. Overall, the distribution of primary outcome scores shifted consistently in favor of the intensive strategy, with a common OR for lower scores of 1.86 (95% CI, 1.22 to 2.83; P = .003). The mean hospital stay for the moderate group was 12.4 days vs 10.9 days in the intensive group (absolute difference, -1.5 days; 95% CI, -3.1 to -0.3; P = .04). The mean ICU stay for the moderate group was 4.8 days vs 3.8 days for the intensive group (absolute difference, -1.0 days; 95% CI, -1.6 to -0.2; P = .01). Hospital mortality (2.5% in the intensive group vs 4.9% in the moderate group; absolute difference, -2.4%, 95% CI, -7.1% to 2.2%) and barotrauma incidence (0% in the intensive group vs 0.6% in the moderate group; absolute difference, -0.6%; 95% CI, -1.8% to 0.6%; P = .51) did not differ significantly between groups.Among patients with hypoxemia after cardiac surgery, the use of an intensive vs a moderate alveolar recruitment strategy resulted in less severe pulmonary complications while in the hospital.clinicaltrials.gov Identifier: NCT01502332.
Health behaviors (HB) and geriatric assessment (GA) in older women with breast cancer (BC).
Authors: Trevor Augustus Jolly, Allison Mary Deal, Shani Malia Alston, Brittaney-Belle Elizabeth Gordon, Samara Ann Dixon, Grant Richard Williams, Hyman Bernard Muss
Journal: Journal of Clinical Oncology (2013)

9543 Background: Physical inactivity (PI), alcohol (A) and tobacco (T) abuse are associated with poor health outcomes in older adults, however, little is known about the prevalence of these HB and their associations with GA domains in older cancer patients (pts). This study explores the relationship between HB and GA in older BC pts. Methods: Between 03/2010-01/2013, 111 pts ≥65 yrs completed a predominantly self-administered GA (Hurria et al. Cancer 2005) comprising measures of comorbidity, polypharmacy, cognitive, functional, psychosocial and nutritional status as well as a nine-item HB questionnaire based on the 2006/7 National Health Interview Survey ( www.cdc.gov/nchs/nhis.htm ) assessing PI, A and T use. Fisher’s Exact and Wilcoxon Rank sum test were used to evaluate associations with GA measures. Results: Median age was 72 (range 65-94). Most pts were white (89%), married (61%), retired (86%) and at least high school graduates (96%). 51% never smoked while 45% were former and 4% current smokers. Former/current smokers were more likely than never smokers to have slower gait speeds (Timed “up and go” &gt;14 second; 32 vs 14%; p=.04) and took more daily prescription medications (mean 5 vs. 4; p=.04). 52% of pts consumed at least one alcoholic drink per week (median 3.5). Modest alcohol consumption was associated with less activity of daily living (ADL) impairment (p=.03), lower mean BMI (29 vs. 26 kg/m 2 p=.03) and greater non-prescription medication use (p=.04). 48% never performed vigorous activity and these pts were more likely than those exercising to have one or more functionally impairing comorbidities (p=.03); mainly arthritis. PI correlated with more impairment in both ADL (p&lt;.0001) and instrumental ADL (p=.004). HB were not associated with demographic factors, treatment phase, weight loss, falls, sensory impairment, social activity, anxiety or depression in this dataset. Conclusions: PI, T and A use were common in this cohort of older BC pts and were associated with significant impairments in several GA domains. These findings reinforce the need for interventions to improve HB in older BC pts. Support: Breast Cancer Research Foundation, New York, NY and Lineberger Comprehensive Cancer Center, Chapel Hill, NC.