tbuckley/cabot-search huggingface dataset:
Anti-VEGF therapies, cancer and renal function
Authors: J. Ayllon, N. Janus, V. Launay-Vacher, J. Medioni, G. Deray, C. Isnard-Bagnis, S. Oudard
Journal: Journal of Clinical Oncology (2008)

16001 Background: Anti-VEGF drugs (AVD) are increasingly used and are associated with arterial hypertension (AH) and proteinuria. However, there are no data on the evolution of the glomerular filtration rate (GFR) in patients treated by AVD. Methods: Renal cancer patients (pts) treated with AVD (2nd line and after nephrectomy) between 2004 and 2007 were included. Age, sex, AH, and serum creatinine were retrospectively collected. GFR was estimated with the aMDRD formula. Results: 67 patients were included from the medical oncology department of the Georges Pompidou European Hospital. Mean and median ages were 60.1 and 58, sex-ratio (M/F) 3.5, mean GFR 65.9 mL/min/1.73m2, AH 22.4% before AVD initiation. Pts received Sunitinib (71.6%), Sorafenib (20.9%), Bevacizumab (4.5%) or both Sunitinib and Bevacizumab (3%) for a median duration of 344 days. For the 2 latter groups, the number of pts was too small to be analyzed. Before AVD, 91% and 40.3% of patients had an estimated GFR < 90 and 60 mL/min/1.73m2, respectively. The variations of GFR are presented in Table I. Conclusions: Decreased GFR before initiation of AVD therapy is highly frequent in renal cancer pts after nephrectomy. The decrease of GFR was globally the same whatever the AVD used, Sunitinib or Sorafenib. Pts with pre-existing AH had a dramatically GFR decline. This observation suggests that in addition to AH monitoring after initiation of AVD therapy, a baseline evaluation of GFR is mandatory. We do not know whether correction of pre-existing AH before initiation of AVD therapy may be beneficial with regard to renal function. Table I. Renal function of the patients under AVD Groups N GFR before AVD (mL/min/1.73m2) Variations of GFR (mL/min/1.73m2/year) All pts 67 65.9 −1.37 Sunitinib pts 48 66.7 −1.36 Sorafenib pts 14 70.2 −2.4 AH pts 15 65.2 −17.5 Non AH pts 52 67.2 +3.3 No significant financial relationships to disclose.
Gene expression analysis for prediction of early brain metastasis (BM) in HER2-positive (HER2+) breast cancer patients (pts)
Authors: R. Duchnowska, J. Jassem, M. A. Thorat, A. Morimiya, G. W. Sledge, L. Li, W. Biernat, C. Szczylik, P. S. Steeg, S. S. Badve
Journal: Journal of Clinical Oncology (2008)

1019 Background: BM is a common occurrence in HER2+ breast cancer pts. If the pts most likely to develop BM could be identified, prophylactic strategies might prevent or delay occurrence of this failure. We explored gene expression differences between HER2+ breast cancers with early vs late occurrence of BM. Methods: Study group included 90 HER2+ breast cancer pts, 43 of whom developed BM (BM+): 22 and 21 pts with <3 and >3 yrs in time from diagnosis to BM, respectively; 47 patients had not developed BM (BM-) at the last follow-up. We performed cDNA-mediated annealing, selection, extension, and ligation (DASL) assay (Illumina Corp) for expression of 502 known cancer genes using 200 ng RNA from archived FFPET. T-test with unequal variances was applied after sample median normalization. Differentially expressed genes were analyzed using Ingenuity Pathway Analysis. Results: A binary comparison of BM+ vs BM- revealed 25 differentially expressed genes (p <0.05). For BM+ in <3 yrs vs >3 yrs comparison, 95 genes were differentially expressed with a p value <0.05. Up-regulated gene pathways included Glucocorticoid Receptor, PI3K/AKT & PTEN, IGF-1, P53 and NF-κB. Down-regulated gene pathways were cell cycle G1/S checkpoint regulation, cell-cycle G2/M DNA damage checkpoint, Vitamin D and retinoic acid receptor signaling. Conclusions: Early BM occurrence in HER-2+ breast cancer pts can be predicted by gene expression in primary tumors. Altered cell cycle regulation seems to be particularly important. Analyses are ongoing to generate a gene-expression signature to predict development of BM. No significant financial relationships to disclose.
High-quality basic care and support needed in lung cancer survivors.
Authors: Ping Yang, Roberto P. Benzo, Stephen D. Cassivi, Andrea L. Cheville, Matthew M. Clark, Mariza de Andrade, Jon Ebbert, Connie Fortner, Yolanda I. Garces, Aminah Jatoi, Randolph Marks, David E. Midthun, Tanya Petterson, Katherine M. Piderman, Jeff A. Sloan, Shawn Stoddard, Jason A. Wampfler, Kathleen J. Yost
Journal: Journal of Clinical Oncology (2012)

54 Background: After diagnosis and treatment, lung cancer survivors do not return to a health-related quality of life (QOL) and function comparable to pre-diagnosis levels as observed in other adult cancer survivors. We hypothesize that inadequate attention has been paid to addressing and improving QOL and function among lung cancer survivors. Our primary goal is to evaluate existing symptoms and QOL deficits among lung cancer survivors. Methods: We are evaluating patterns of QOL deficits (scored 5 or less on the scale from 0 [worst] to 10 [best]) in relation to time of lung cancer diagnosis, treatments, progression and/or recurrence, and health-related conditions. We are collecting and analyzing relevant health care utilization for selected QOL deficits, and identifying availability, accessibility, and effectiveness of evidence-based interventions. The expected outcomes will be new knowledge on patterns of QOL deficits, quality-adjusted life years in relation to the availability, accessibility, and adequacy of needed care and the effectiveness of interventions targeting improvement in QOL and symptoms. Results: In our initial analysis, among 3,707 lung cancer survivors who were diagnosed in 1999 to 2010, post-cancer treatment, and followed through 2011, 39% (1,442) reported deficits in overall QOL, 71% fatigue, 60% dyspnea, 41% being sedentary, 17% low spiritual well-being (SWB), and 10% currently smoking cigarettes. Among the 1,442 lung cancer survivors with a deficit in overall QOL, 97.5% reported severe fatigue or dyspnea, being sedentary or smoking, or having low SWB. In the remaining 36 of the 1,442, 24 had pain, cough, poor appetite, or other symptoms; only 12 (&lt;1%) did not report deficit in any of the measured QOL domains. Analyses are ongoing. Conclusions: Based on evidence gained to date, we are developing and testing interventions targeting symptoms and QOL deficits. We expect to gain strong evidence for recommendations in redefining and delivering care and support that are necessary for improving the health and QOL of lung cancer survivors.
Associations between K-ras mutation, smoking, and prognosis of pancreatic cancer.
Authors: Kei Saito, Yousuke Nakai, Hiroyuki Isayama, Takashi Sasaki, Naminatsu Takahara, Tsuyoshi Hamada, Koji Miyabayashi, Keisuke Yamamoto, Suguru Mizuno, Dai Mohri, Hirofumi Kogure, Natsuyo Yamamoto, Kenji Hirano, Hideaki Ijichi, Keisuke Tateishi, Minoru Tada, Kazuhiko Koike
Journal: Journal of Clinical Oncology (2014)

298 Background: Smoking is recognized as a risk factor for pancreatic cancer, but its associations with prognosis are not fully elucidated. Smoking was associated with poor outcomes in colon cancer, especially in patients with K-ras mutation (J Clin Oncol. 2013;31:2016-23). Therefore, we conducted this retrospective analysis of the associations of K-ras mutation, smoking and prognosis in patients with pancreatic cancer. Methods: Patients with pancreatic cancer who received surgery or chemotherapy at the University of Tokyo Hospital were retrospectively studied. The prognosis of patients with mutant and wild K-ras were compared. Overall survival was evaluated using Kaplan-Meier methods and compared by long-rank test. Cox regression models were used to calculate hazard ratios (HRs) to evaluate the prognostic factors in patients with pancreatic cancer with mutant K-ras or wild K-ras. Results: Between January 2009 and August 2013, K-ras mutation analysis was evaluated in 187 patients (47 surgical resection and 140 chemotherapy). K-ras mutation was detected in 74.3%. The rates of current-, ex- and never-smokers were 18.2%, 31.6% and 50.3%, respectively. In patients with mutant K-ras, the rate of male gender (46.0% vs. 29.0%), presence of distant metastasis (50.4% vs. 31.3%) and median CA19-9 (374 U/mL vs. 136 U/mL) were significantly higher than that in patients with wild K-ras. The rate of ever smokers (current- and ex-smokers) did not differ significantly (48.2% in mutant K-ras vs. 56.3% in wild K-ras, p=0.403). Median survival time (MST) was 16.7 (95%CI, 11.9-21.8) months in patients with mutant K-ras, compared with 20.3 (95%CI, 15.8-34.6) in patients with wild K-ras (p=0.193). Meanwhile, MST was 22.2 (95%CI, 16.9-27.9) vs. 14.8 (95%CI, 9.1-19.4) months in patients with and without smoking (p=0.024). After adjustment by age, gender, performance status, CA19-9 and treatment, HRs of smoking were 1.96 (95%CI, 1.06-3.68, p=0.032) in patients with mutant K-ras, but the association was not significant in patients with wild-K-ras (HR 1.35 [95%CI, 0.37-5.28], p=0.653). Conclusions: As previously reported in colon cancer, smoking was associated with poor prognosis in pancreatic cancer with K-ras mutation.
Difference in strong opioid prescription among different cancer and care providers in advanced cancer patients in Taiwan: Analysis using national health insurance database.
Authors: Ruey Kuen Hsieh, Yu-Lin Lin, Chao-Hsiun Tang
Journal: Journal of Clinical Oncology (2015)

55 Background: Pain assessment and management had been adopted as an important criteria in hospital accreditation in Taiwan. National health insurance database may help to determine factors influencing patterns of strong opioid use in advanced cancer patients in their final 12 months of life. Methods: Cancer patients who died from cancer during 2008-2011 were included in the analysis. Data in prescription of strong opioids during their last 12 months of life were collected and analyzed using National Health Insurance Research Database (NHIRD). Patient’s characteristics, such as cancer types, birthdate and gender, as well as information on the provider’s characteristics, such as specialty, gender and age of the physician, the ownership and level of accreditation of the hospital, and the level of urbanization of the hospital where it is located, were also retrieved and included as the controlled variables in the analysis. Results: Of the 162,679 cancer deaths, 57,578 were prescribed strong opioids in their last year of life (35.4 percent). Strong opioid prescription steadily decreased with the corresponding increase in patient age. Besides there are difference in different cancer types. Association with prescription prevalence has also been noted among physician characteristics such as subspecialty, gender and age, as well among hospital characteristics, such as public vs private and accreditation level. Conclusions: There are significant difference in strong opioids prescription among different care providers for advanced cancer patients. Information from this study can guide further efforts in improving supportive care and education for advanced cancer care providers.
Effect of diet on bladder cancer survivors.
Authors: Thomas Andrew Longo, Ajay Gopalakrishna, Joseph J Fantony, Brant Allen Inman
Journal: Journal of Clinical Oncology (2016)

437 Background: Diet has been shown to affect cancer recurrence, progression, and overall survival. A reduction in overall mortality is associated with high intake of vegetables and whole grains, but little is known about the role of other macronutrients. Further, the role of macronutrients in bladder cancer survivors as they move beyond the treatment period is unknown. Methods: After IRB approval, an institutional database was used to identify a large cohort of bladder cancer patients. They were mailed a survey that included the Diet History Questionnaire II (DHQ II). This validated instrument is recommended by the American Cancer Society and National Cancer Institute. It involves 151 questions covering portion size over 134 food items and 8 supplements, and takes a patient roughly an hour to complete. Our cross-sectional survey used the results from the DHQ II to assess compliance with the US Dietary Guidelines for Americans. Results: Out of 962 subjects, 461 completed the survey (48%). Mean age was 73, 80% were male, and 87% were white. The recommended protein intake was met or exceeded 98% of respondents and 66.8% were able to meet the fruit and vegetable recommendations. Similarly, 62.9% met carbohydrate recommendations. Unfortunately, only 44.5% met fat recommendations, and 0.9% met the whole grain recommendations. Recommended sodium intake was exceeded by 62% of subjects. Conclusions: Bladder cancer survivors exhibit poor adherence to standard dietary recommendations, but they represent a unique metabolic state. It is unknown what constitutes a healthy diet in a bladder cancer survivor, but a healthy diet has potential to be a component of survivorship intervention and not merely sustenance. Cancer survivors are an important target population for health promotion efforts and we plan further investigation of diet and its impact on quality of life amongst other lifestyle factors.
Effect of VTE on mortality in patients with stage III colon cancer.
Authors: C. D. Mullins, K. A. Bikov, D. L. McNally, N. C. Onwudiwe, M. R. Dalal, N. Hanna
Journal: Journal of Clinical Oncology (2011)

3620 Background: Management of stage III colon cancer (SIIICC) frequently focuses on cancer-specific survival, yet overall survival and adverse events also impact the net clinical benefit of cancer management strategies. Furthermore, there are evidence gaps surrounding overall survival among elderly patients. Methods: A retrospective cohort analysis examined all-cause survival among incident SIIICC patients within Surveillance, Epidemiology, and End Results (SEER)-Medicare data for patients diagnosed between 2004 and 2005 with follow-up through 2007. Medicare parts A&B (without Medicare HMO) was required to avoid missing claims data. Patients were censored due to death, end of simultaneous enrollment in Medicare parts A&B, or enrollment in an HMO. Patient descriptive characteristics and outcomes were examined using chi-square and t-tests; adjusted survival analyses used Cox proportional hazards regressions. Results: There were 4,985 SIIICC patients, of whom 1,033 (20.7%) were diagnosed with VTE following SIIICC diagnosis. African-Americans, urban residents, and those with higher CCI scores or VTE in the year before SIIICC diagnosis were more likely to have a VTE following their cancer diagnosis. VTE patients had significantly higher mortality (48.75% vs. 43.05%, p < 0.01). Multivariate analyses controlling for clinical and demographic factors showed that patients with VTE were 26% (CI: 14.1% – 39.6%) more likely to die. Other significant predictors of mortality included older age, poor performance status at baseline, CCI =2+, treatment with chemotherapy or monoclonal antibodies. Conclusions: VTE following diagnosis of stage III colon cancer diagnosis is a significant predictor of death. Among elderly Americans diagnosed with stage III colon cancer, the increased hazard of death due to VTE was 26%. Hazard ratio 95% CI Age at cancer diagnosis (Ref 66-75) 75 ≤ 80 1.205 1.063 1.366 80 ≤ 85 1.384 1.224 1.565 85 + 1.499 1.316 1.709 CCI CCI=1 vs. CCI=0/unknown 1.004 0.904 1.115 CCI=2+ vs. CCI=0/unknown 1.174 1.042 1.323 Proxy for poor performance status Yes vs. No 1.194 1.081 1.318 Treated with chemotherapy and/or monoclonal antibody Yes vs. No 0.587 0.532 0.648 VTE diagnosis within the observation period Yes vs. No 1.262 1.141 1.396
Factors predictive of tumor recurrence and overall survival in patients with esophageal cancer who have pathologic complete response after neo-adjuvant therapy.
Authors: Alexandra Gangi, Sarah E. Hoffe, Jessica M. Frakes, Khaldoun Almhanna, Luis Pena, Jacques Fontaine, Aaron Udell Blackham, Jose Mario Pimiento
Journal: Journal of Clinical Oncology (2016)

170 Background: Pathologic complete response (pCR) to neoadjuvant therapy is presumably associated with favorable outcomes in patients (pts) with esophageal cancer, but reported survival rates vary. This study evaluates patterns of recurrence after curative esophagectomy and identifies factors predictive of recurrent disease and overall survival (OS) in patients with pCR. Methods: An IRB-approved, retrospective review of a prospective esophageal cancer database was conducted. Patient demographics, perioperative data, and outcomes were examined. Recurrences were classified as locoregional (LR) or systemic. Cox regression model and Kaplan–Meier (KM) plots were used for survival analysis. Results: 837 pts with invasive esophageal cancer treated at a single institution from 1994 to 2013 were identified. 176 pts underwent neoadjuvant therapy followed by surgery and had pCR. Of these, 93.7% had adenocarcinoma and 6.3% had squamous cell cancer. Mean age was 56.6 and most pts were white (96.6%) males (79.5%). Median follow up was 42.6 months. 95 pts were treated before 2007 and 81 after. Most pts (85%) underwent transthoracic esophagectomy. All 176 pts received chemotherapy and radiation; dose-specific information was available on 144 pts, of whom most received 50.4 Gy (45%). 170 pts had recurrence data available: 39 (22.9%) had recurrent disease at a mean of 18.3 months; 5 (2.9%) with LR and 34 (20%) with systemic disease. On multivariate analysis, when evaluating patient demographics, pretreatment stage, type of surgery, type of chemotherapy, and number of lymph nodes resected, only pretreatment stage was associated with recurrence (p = 0.04). Median time to recurrence was 26.3 months for LR disease and 10.9 months for systemic disease (p = 0.3). KM estimates determined that pre-treatment stage and time of treatment ( &lt; 2007 or ≥ 2007) were predictive of improved OS (p &lt; 0.01, = 0.03). Conclusions: The incidence of disease recurrence in pts who experience pCR is low. The pretreatment stage and time of treatment were independent predictors of improved OS. Enhancing treatment strategies to maximize pCR would improve outcomes in pts with esophageal cancer.
Phase I study of topotecan continuous infusion and weekly cisplatin with radiation therapy for locally advanced/recurrent cervical cancer
Authors: L. A. Padilla, S. K. Mitchell, L. F. Carson
Journal: Journal of Clinical Oncology (2005)

5129 Background: Topotecan is a topoisomerase -1 inhibitor with radiosensitizing effects. The combination of topotecan with cisplatin has shown clinical activity against cervical cancer. Methods: Patients with stages IB2- IVA or recurrent cervical cancer who had not received prior radiation or chemotherapy were eligible. Topotecan was administered as a continuous I.V. infusion for 5 days each week through a central venous catheter. Dose levels evaluated were 0.05 (n= 7), 0.1 (n=7) and 0.15 (n= 5) mg/m2 / day. Cisplatin was administered I.V. weekly at 20 mg/m2. Conventional doses of pelvic and para-aortic radiation were administered. Results: Ninety seven, 92 and 96% of all cycles for each dose level were administered on schedule. Onlythree patients did not complete the full treatment course: one due to noncompliance and two due to grade 4 thromboembolic complications (one patient in dose level 1 with a septic superior vena cava thrombus leading to death and another in dose level 3 with a pulmonary embolus). The most common hematologic toxicity was grade 3 lymphopenia (n=9). Only one patient experienced grade 3 neutropenia. Of 3 delayed weekly cycles, none were due to hematologic toxicity. Other main toxicities included: grade 3 leukopenia (n=6), grade 3 coagulation (n=1), grade 3 fatigue (n=2), grade 3 G.I. (n=3), lymphocysts (n=2), non-neutropenic fever (n=2). Six patients required blood transfusion during therapy. Only 3 patients required r-erythropoetin. Only one patient had persistent disease diagnosed within the six months following completion of treatment while the rest had complete responses. Conclusions: The administration of 0.15 mg/m2/day topotecan as a continuous infusion in conjunction with cisplatin and radiation is reasonably well tolerated and appears clinically active in advanced cervical cancer. Thromboembolic complications, frequent in cervical cancer patients, may lead to alternative delivery methods in future clinical trials. No significant financial relationships to disclose.
Neoadjuvant chemoradiation for fixed cT3 or cT4 rectal cancer: Results of a Polish II multicentre phase III study.
Authors: Krzysztof Bujko
Journal: Journal of Clinical Oncology (2016)

489 Background: The study tested whether preoperative 5x5 Gy and consolidation chemotherapy is more locally efficacious than standard preoperative chemoradiation in “unresectable” cancer (ClinicalTrials.gov NCT00833131). Methods: Patients with fixed cT3 or cT4 rectal cancer without distant metastases were randomized either to 5x5 Gy and 3 courses of FOLFOX4 after one week rest (experimental group) or to 50.4 Gy delivered in 28 fractions given simultaneously with a 5-Fu bolus, leucovorin and oxaliplatin (control group). For the second study part, oxaliplatin was delivered to the two groups at the discretion of the participating centre. Both groups underwent surgery about 12 weeks after starting radiation and about 6 weeks after neoadjuvant treatment. Results: 515 patients were eligible for analysis; 261 in the experimental group and 254 in the control group. Acute toxicity of neoadjuvant treatment was recorded in 74% of patients in the experimental group and in 83% in the control group, p = 0.007; the rate of patients with grade 3+ toxicity was identical in the two groups - 24%. R0 resection rates (primary endpoint) and pathological complete response rates were respectively in the experimental group and in the control group 77% vs. 71% (p = 0.081) and 16% vs. 11.5% (p = 0.19). Median follow-up was 35 months. At 3 years, rates of overall survival, disease-free survival and cumulative incidence of local failure were respectively in the experimental group and in the control 73% vs. 64.5%, p = 0.055; 53% vs. 52%, p = 0.74 and 22% vs. 21%, p = 0.82. Conclusions: The trial showed no difference in local efficacy between preoperative 5x5 Gy with consolidation chemotherapy and standard preoperative chemoradiation. The trend towards improved overall survival, lower toxicity, lower cost and convenience favors 5x5 Gy with consolidation chemotherapy. Clinical trial information: NCT00833131.