tbuckley/cabot-search huggingface dataset:
Docetaxel (D) consolidation therapy following cisplatin (P), vinorelbine (V) and concurrent thoracic radiotherapy (TRT) in patients with unresectable stage III non-small cell lung cancer (NSCLC)
Authors: I. Sekine, H. Nokihara, M. Sumi, N. Saijo, Y. Nishiwaki, S. Ishikura, K. Mori, I. Tukiyama, T. Tamura
Journal: Journal of Clinical Oncology (2005)

7125 Background: To evaluate feasibility and efficacy of docetaxel consolidation therapy after concurrent chemoradiotherapy for unresectable stage III NSCLC. Methods: Patients with PS 0–1 and no prior therapy were treated with P (80 mg/m2 on days 1, 29, 57), V (20 mg/m2 on days 1, 8, 29, 36, 57, 64), and TRT (60 Gy/30fr over 6 weeks starting on day 2), followed by consolidation D (60 mg/m2 every 3–4 weeks for 3 cycles). Results: Of 97 patients enrolled between April 2001 and June 2003, 93 were evaluable. There were 76 males and 17 females with median age of 60 (range 31–74) and weight loss less than 5% in 77 patients, and 41 stage IIIA and 52 IIIB diseases. Chemoradiotherapy was well tolerated; 3 cycles of PV and 60Gy of TRT were administered in 80 (86%) and 87 (94%) patients, respectively. Grade 3–4 neutropenia, esophagitis, and pneumonitis were developed in 62, 11, and 3 patients, respectively. Docetaxel consolidation was administered in 59 (63%) patients, but 3 cycles were completed in only 34 (37%) patients. Reasons for discontinuation were progressive disease in 3, pneumonitis in 14, esophagitis in 1, other toxicity in 3, and patient refusal in 4 patients. During consolidation therapy, grade 3–4 neutropenia, esophagitis, and pneumonitis were developed in 51, 2, and 4 patients, respectively. Late toxicity was noted in 32 patients. Grade 3–4 pneumonitis and esophagitis were developed in 4 and 2 patients, respectively. Four patients died of pneumonitis. The response rate was 82% (95%CI 73–88) with 5 CRs and 71 PRs. The median progression-free survival was 12.8 months, and median survival was 30.8 months. Conclusions: This regimen produced promising median survival in patients with stage III NSCLC, but compliance of docetaxel consolidation was very poor. No significant financial relationships to disclose.
PTEN/AKT Pathway Mutations Are Reciprocal to NOTCH-Activating Mutations In Pediatric T-Cell Acute Lymphoblastic Lymphoma (T-ALL)
Authors: Linda Zuurbier, Maartje Vuerhard, Clarissa Kooi, Willem K Smits, Jessica Buijs-Gladdines, Martin A. Horstmann, Válerie de Haas, Rob Pieters, Jules Meijerink
Journal: Blood (2010)
Efficacy of new agents on advanced castration-refractory prostate cancer with RAPID progression.
Authors: Shenhong Wu
Journal: Journal of Clinical Oncology (2014)

257 Background: Five new agents with diverse mechanisms of action have been shown to improve overall survival for patients with advanced castration-refractory prostate cancer (CRPC). Because of a heterogeneity in cancer growth and proliferation, it is not clear whether these agents are effective in patients with rapid progressive disease. Therefore, we conducted a systematic review and meta-analysis of published randomized controlled clinical trials (RCTs) to assess the effect of these new agents on three month progression and mortality. Methods: Databases from PUBMED, the Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until June, 2013 were searched to identify relevant studies. Early progression was defined as progressive disease or death at three months after the initiation of clinical trial. Eligible studies included prospective RCTs in which a new agent was compared to a control in metastatic CRPC patients. Summary incidences of three month progression or mortality, relative risk (RR), and 95% confidence interval (CI) were calculated based on the heterogeneity of included studies. Results: A total of 5,895 patients (new agents: 3,623, control: 2,272) with CRPC from seven RCTs were included for analysis. The new therapy significantly reduced the risk of mortality in the overall patient population (HR=0.69, 95% CI: 0.64-0.74) without significant variation among different agents (P=0.82). The new therapy also reduced the risk of three month mortality (RR=0.76, 95% CI: 0.60-0.97, P=0.027). However, significant risk reduction was only seen for enzalutamide (RR=0.54, 95% CI: 0.31-0.94; P=0.03). In addition, the new therapy reduced the risk of three month progression (RR=0.61, 95% CI: 0.46-0.81, P=0.001). The risk varied among these agents (P&lt;0.001), with significant risk reduction seen for enzalutamide (RR=0.47, 95% CI: 0.21-0.54), abiraterone (RR=0.57, 95%CI: 0.35-0.97), and cabazitaxel (RR=0.80, 95% CI: 0.72-0.89), but not for Sipuleucel-T (RR=1.10, 95% CI: 0.21-5.76). Conclusions: The new agents may have a differential impact on the outcome of CRPC with rapid progression.
The role of nursing in obtaining a three-generation familial cancer history intake tool (FCHT) and the care of patients with hereditary gastrointestinal syndromes.
Authors: Lucia Fontes-Borts, Howard Safran, Kimberly Perez
Journal: Journal of Clinical Oncology (2014)

216 Background: Of patients diagnosed with colorectal cancer, 5-10% of all cancers are associated with hereditary cancer syndromes. Since hereditary gastrointestinal cancer syndromes convey a markedly increased risk for developing cancer, identification of affected families is important. Studies have found that clinicians are unlikely to adequately or routinely collect family history information on their patients. This study assessed the implementation of a validated three-generation family history intake tool by an advanced practiced nurse practitioner (APNP) and the impact on clinical practice at a mid-size academic affiliated Medical Oncology practice. Methods: From September 2013 to January 2014, 100 patients with the diagnosis of colorectal cancer were assessed after a clinic session with a physician by an APNP. The APNP utilized a validated 3 - generation family history tool. Information regarding age, sex, education, annual income, family ethnicity, diet, exercise and previous genetic testing was also collected. Data collected was then analyzed to assess risk of hereditary syndrome. A chart review of the patients was performed to analyze microsatellite instability testing and prior genetic counseling referrals. Results: Of the 100 screened, 93 patients were evaluable. There were 52 males: 39 female participants with a median age of 60.71 years (range 28-90). The implementation of FCHT was associated with an increase in identification of individuals at risk; 16 (17.2%) patients reported a diagnosis of CRC at age less than 50. The rate of referrals for genetic evaluation tripled after the implementation of the FCHT (6.5% to 16.3%). Of the 17 referred, five had been referred prior to implementation of the FCHT. Conclusions: Institution of a separate session with an APNP to assess family history resulted in a 3-fold increase in rates of detection of patients with high risk for hereditary cancer syndromes associated with colorectal cancer.This study demonstrates that APNP’s are well positioned to promote preventative health by engaging in family history intake and genetic assessment referral.
Socioeconomic status and recurrent emergency visits amongst chemotherapy patients.
Authors: Priyanka Kapil, Katherine Enright
Journal: Journal of Clinical Oncology (2014)

106 Background: Multiple studies have found that cancer patients undergoing cytotoxic chemotherapy have a high rate of emergency department (ED) utilization throughout the course of their treatment and up to 20% of patients have recurrent ED visits. We assessed the effect of socioeconomic status (SES) on recurrent ED visits for infectious causes amongst chemotherapy patients. Methods: All patients who visited the Peel Regional Cancer Centre ED within 30 days of receiving cytotoxic chemotherapy between 04/12 - 3/13 were identified. Patients were included in the study if their primary reason for presentation was either fever or infection. Postal codes were cross-matched against 2011 census data from Statistics Canada to obtain estimates of income, education, and occupation. The impact of SES factors on the likelihood of multiple ED visits was analyzed. Results: 239 patients with at least 1 visit to the ED for infection were identified. Of these patients 103 (43.1%) had recurrent ED visits. Patients from areas with a higher proportion of arts, sports, culture, recreation, agriculture, and natural resources employment had a significantly (p&lt;0.02) lower incidence of recurrent visits compared to single visits. Patients from areas with a lower proportion of healthcare, natural sciences, and applied sciences employment had a significantly (p&lt;0.04) lower incidence of recurrent visits compared to single visits. Patients from areas with a greater proportion of people for whom the highest education completed was only high school had a significantly (p= 0.01) lower incidence of recurrent visits compared to single visits. Conclusions: Instead of observing a higher rate of ED visits for infection among patients with lower SES, patients residing in areas of lower education or in areas with a higher proportion of employment in fields associated with lower SES were less likely to have recurrent visits. It remains unclear if this represents decreased adherence to fever recommendations in patients with lower SES or over usage of ED services in patients with higher SES. Further studies are planned to better understand these observations to help inform educational interventions and community-based monitoring aimed at decreasing the risk of ED visits.
Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting
Authors: Pradeep Natarajan, Robin Young, Nathan O. Stitziel, Sandosh Padmanabhan, Usman Baber, Roxana Mehran, Samantha Sartori, Valentin Fuster, Dermot F. Reilly, Adam Butterworth, Daniel J. Rader, Ian Ford, Naveed Sattar, Sekar Kathiresan
Journal: Circulation (2017)

Relative risk reduction with statin therapy has been consistent across nearly all subgroups studied to date. However, in analyses of 2 randomized controlled primary prevention trials (ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm] and JUPITER [Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin]), statin therapy led to a greater relative risk reduction among a subgroup at high genetic risk. Here, we aimed to confirm this observation in a third primary prevention randomized controlled trial. In addition, we assessed whether those at high genetic risk had a greater burden of subclinical coronary atherosclerosis.We studied participants from a randomized controlled trial of primary prevention with statin therapy (WOSCOPS [West of Scotland Coronary Prevention Study]; n=4910) and 2 observational cohort studies (CARDIA [Coronary Artery Risk Development in Young Adults] and BioImage; n=1154 and 4392, respectively). For each participant, we calculated a polygenic risk score derived from up to 57 common DNA sequence variants previously associated with coronary heart disease. We compared the relative efficacy of statin therapy in those at high genetic risk (top quintile of polygenic risk score) versus all others (WOSCOPS), as well as the association between the polygenic risk score and coronary artery calcification (CARDIA) and carotid artery plaque burden (BioImage).Among WOSCOPS trial participants at high genetic risk, statin therapy was associated with a relative risk reduction of 44% (95% confidence interval [CI], 22-60; P<0.001), whereas in all others, the relative risk reduction was 24% (95% CI, 8-37; P=0.004) despite similar low-density lipoprotein cholesterol lowering. In a study-level meta-analysis across the WOSCOPS, ASCOT, and JUPITER primary prevention, relative risk reduction in those at high genetic risk was 46% versus 26% in all others (P for heterogeneity=0.05). Across all 3 studies, the absolute risk reduction with statin therapy was 3.6% (95% CI, 2.0-5.1) among those in the high genetic risk group and 1.3% (95% CI, 0.6-1.9) in all others. Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04-1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2-17.8) burden of carotid plaque.Those at high genetic risk have a greater burden of subclinical atherosclerosis and derive greater relative and absolute benefit from statin therapy to prevent a first coronary heart disease event.URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00738725 (BioImage) and NCT00005130 (CARDIA). WOSCOPS was carried out and completed before the requirement for clinical trial registration.
Large-scale analysis for treatment strategy according to genetic alterations of KRAS and DPC4 (SMAD4) genes in pancreatic ductal adenocarcinoma.
Authors: Sang Hyun Shin, Song Cheol Kim, Ki Byung Song, Jae Hoon Lee, Dae Wook Hwang, Dong Joo Lee, Jung Woo Lee, Hyoung Eun Kim, Eunsung Jun, Kwang-Min Park, Young-Joo Lee
Journal: Journal of Clinical Oncology (2015)

361 Background: To investigate correlation of genetic alterations of pancreatic ductal adenocarcinoma (PDAC) with patients’ survival, recurrence patterns, and treatment for recurrent disease. Methods: We reviewed genetic alterations of major 4 genes (K-ras, DPC4, p53, and c-erbB-2) in 699 patients who underwent surgical resection, and correlated with clinical outcomes. Results: Median survival of all patients was 21.7 months, and 5-year survival rate was 20.4%. Alterational rates of each gene were as follows: K-ras, 48.3%; DPC4, 68.1%; p53, 40.8%; c-erbB-2, 14.0%. Mutation of K-ras and inactivation of DPC4 genes were associated with shorter patients’ survival in univariate analysis. In multivariate analysis, mutation of K-ras gene was independently correlated with patients’ survival (especially, GAT and TGT subtypes). Inactivated DPC4 gene had no independent correlation with overall survival, but it was strongly associated with distant metastasis following pancreatectomy. Survival after recurrence (SAR) was evaluated in subdivided groups according to DPC4 gene function (intact or loss)/recurrence patterns (locoregional or distant)/treatment options (local control or systemic therapy). In these 8 groups, patients in intact/locoregional/local control group showed the longest survival (24.2 months of median SAR), and intact/locoregional/systemic therapy and loss/distant/systemic therapy groups were associated with much shorter survival (9.5 and 9.2 months of median SAR, respectively). Conclusions: Assessment of genetic features of PDAC may assist in deciding targeted surveillance or treatment for primary as well as recurrent PDAC, and further studies for therapeutic strategies according to genetic analyses should be devised.
Cell cycle and apoptotic effects of PM00104 in pediatric cell lines and xenographs.
Authors: A. Beaugrand, C. Lanvers-Kaminsky, P. M. Aviles Marin, C. Cuevas Marchante, P. Opolon, L. Le Dret, A. Verschuur, G. Vassal, B. Geoerger
Journal: Journal of Clinical Oncology (2011)

9546 Background: PM00104 (Zalypsis) is a new synthetic alkaloid related to jorumycin and the renieramycins with in vitro growth-inhibitory properties in the low nanomolar range and anti-tumor activity in vivo against several adult cancers. Methods: This preclinical study within the European Innovative Therapies for Children with Cancer consortium explored PM00104 in pediatric malignancies (leukemia, neuroblastoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, and medulloblastoma). Results: PM00104 exhibited cytotoxicity against all 24 cell lines tested in a dose dependent manner with mean IC50s of 3 nmol/L as measured by MTS proliferation assay. In RD rhabdomyosarcoma xenografts, PM00104 administered intravenously at 0.8 and 1.0 mg/kg once weekly during 4 weeks resulted in 100% tumor regression and significant tumor growth delay of 42 and 38 days, respectively, compared to controls (p<0.01; Kruskal-Wallis test). In SJ-NB-8 and SH-SY5Y neuroblastomas, PM00104 at 1.0 mg/kg yielded significant growth delays (7.2 and 9.9 days, respectively; p=0.0002; Mann-Whitney test) without tumor regression. PM00104 induced TP53 expression but its activity occurred independent of the TP53 status. In the highly sensitive RD cells, PM00104 induced prolonged G2/M cell cycle arrest and apoptotic cell death as determined by annexin V, caspase 3, caspase 9, and PARP-1 cleavage. Both caspase 8-deficient neuroblastoma cells underwent significant rapid cell death mainly unrelated to apoptosis with few caspase 3 and absence of caspase 9 cleavage. Neuroblastoma cells expressed high levels of IL-6R, and IL-6 mediated immune response may alter PM00104 activity in vivo. Conclusions: PM00104 exhibits cytotoxic activity against pediatric cancer cell lines and xenografts. Significant antitumor activity in vivo was associated with G2/M cell cycle arrest, induction of apoptosis and lack of IL-6R expression.
Pancreatic cancer: Survival in clinical trials versus the real world.
Authors: Reith Roy Sarkar, Rayna Matsuno, James Don Murphy
Journal: Journal of Clinical Oncology (2016)

216 Background: Physicians often use clinical trial data to estimate expected survival for their patients, however clinical trial results may not generalize to a broader population. Given the need for accurate prognostication, we examined whether the survival of clinical trial pancreatic adenocarcinoma patients was similar to “real world” patients. Methods: We conducted a literature search using Pubmed to identify pancreatic adenocarcinoma Phase III trials published between 2005 and 2012. We excluded secondary or pooled analyses, trials with second-line treatments, and non-randomized studies. We compared clinical trial patients to a cohort of patients from the Surveillance, Epidemiology, and End Results (SEER) program, matching for diagnosis year, age and stage of disease. We evaluated for differences in median survival, 1-year survival, and 2-year survival. Results: We identified 27 trials (3 metastatic, 16 mixed metastatic and locally advanced, 3 locally advanced, and 5 resectable) that fit our search criteria, consisting of 8,438 patients. Compared to SEER the median survival was higher in 98% of the individual clinical trial arms by an average of 3.7 months (p = 0.001). The 1-year overall survival rate was higher in 100% of the clinical trial arms by an average of 12.3% (p &lt;.0001). The 2-year overall survival was higher in 76% of the clinical trial arms by an average of 5.1% (p &lt;.0001). The survival differences between SEER and clinical trials were greatest for patients with metastatic pancreatic cancer. Conclusions: We found that clinical trial patients have profoundly improved survival compared to patients in the SEER database, suggesting that clinical trial survival estimates may not generalize to “real world” patients with pancreatic cancer. Patient performance status, underlying comorbidity, and differences in treatment could not be assessed in SEER, though these factors likely explain a portion of the survival differences. These findings suggest that physicians should use caution when extrapolating survival estimates from clinical trials to the real world.
Epidemiology of NSCLC in a Costa Rican hospital: 2003-2008.
Authors: L. Corrales-Rodriguez, D. U. Landaverde
Journal: Journal of Clinical Oncology (2011)

e12000 Background: Lung cancer has increased in incidence and mortality in the past years. In Costa Rica, the incidence and overall mortality rate of lung cancer is practically the same: 8/100,000 people. Differentiation between squamous and nonsquamous histology is of extreme importance in NSCLC for further molecular investigation and treatment decisions. Epidemiologic differences between histologies have been described where subsets of patients may benefit from a specific treatment approach. There is limited information of NSCLC epidemiology in Latin American populations. This retrospective epidemiologic study analyzed NSCLC in the population treated at Hospital San Juan de Dios (HSJD) in San José, Costa Rica. This is the first study performed in Costa Rica assessing epidemiology and overall survival in NSCLC. Methods: Records of patients diagnosed with NSCLC were obtained from the HSJD from Jan 2003 to Dec 2008. 233 cases were identified, only 89 patients were included in the study. Overall survival (OS) and the relationship between histology, stage, and chemotherapy was analyzed with measurements of position (modes and medians) and Kaplan-Meier method. Results: See table. Additionally, there was no statistically significant difference between histologic subtypes in OS for stage IIIB- IV treated patients. Conclusions: Mortality of NSCLC in Costa Rica is high. Most patients are diagnosed in advanced stages (IIIB-IV). Relatively high percentage of patients were nonsmokers; therefore genetic mutations could play a role in etiology. Squamous cell carcinoma is the most common histology. Cisplatin-paclitaxel improved significantly overall survival independent of histologic subtype. Characteristics of patients diagnosed with NSCLC between 2003 and 2008 in HSJD, Costa Rica (n=89). CI=95% P value Gender (n) Men 58 Women 34 Median age (y) 64.9 Nonsmokers (%) 21 Histology (%) Squamous 42 Adeno 35 LC 11 NOS 12 Stage IIIB-IV (%) 79 4 or + cycles of CT (%) 73 Median OS (m) IIIB With CT 13.3 7.9-18.7 Without CT 2.3 1.5-3.2 p=0.005 IV With CT 8.9 6.8-11.0 Without CT 1.8 0.5-3.1 p=0.025 Adeno With CT 10.2 4.1-17.3 Without CT 2.2 0.7-2.6 Squamous With CT 15.4 4.3-26.5 Without CT 1.3 0.8-1.4 LC With CT 6.5 0.8-12.2 Without CT 0.5 0.3-0.8 NOS With CT 11.3 7.5-15-2 Without CT 1.0 0.4-1.7
Targeted therapy in gastrointestinal stromal tumor (GIST): A nationwide database analysis from Taiwan.
Authors: I-Jen Chiang, Wen-Yi Shau, Wei-Tse Fang, Chi-Hui Fang, Yen-Yang Chen
Journal: Journal of Clinical Oncology (2014)

437 Background: Gastrointestinal stromal tumor (GIST) is a visceral sarcoma that arises from the gastrointestinal tract. Currently, imatinib (first-line) and sunitinib (second-line) are two reimbursed targeted therapies for GIST in Taiwan. This study aimed to evaluate the real world data of targeted therapies in GIST treatment among Taiwanese population. Methods: We conducted a nationwide retrospective cohort study based on data from the National Health Insurance Research Database (NHIRD) between January 2005 and December 2010. NHIRD is a comprehensive database of administrative and claim data which covers over 99% of entire population in Taiwan. Patients were selected with ICD codes and targeted therapy utilization, imatinib (IMA) or sunitinib (SUN). Time to treatment discontinuation (DC) due to any reasons (such as death, intolerance and disease progression) was estimated using Kaplan-Meier analysis. Results: From 2005 to 2010, the incidence rate of GIST in Taiwan was between 20 and 30 cases per million. A total of 3,436 GIST patients were identified; the mean age was 63.2 years and 57 % were male. Most patients (94.7%) received standard dose IMA (…400mg/day). Among these patients, 136 patients (4.0%) required IMA dose escalation and 44 (1.3%) patients switched to SUN after IMA. The probability of the 1st-line treatment DC was 20%, 30.7%, 38.9%, 43.2%, and 47.1% for years 1 to 5, respectively. The probability of a change in treatment pattern (defined as either IMA dose escalation or switch to SUN) was 4% 6.8%, 9.6%, 10.5% and 11.7% for years 1 to 5. Lastly, the probability of the 2nd-line treatment DC was 20.5%, 33.7%, 41.1%, 44.8%, 51.7% for years 1 to 5, respectively. Conclusions: First-line IMA plus other treatment modalities may provide additional benefits to progression-free survival. Taiwanese GIST patients who failed first-line treatment still gained benefit from either IMA dose escalation or a switch to SUN. Additional analysis is required for the detailed comparison in different treatment patterns.