tbuckley/cabot-search huggingface dataset:
Colorectal cancer inherited susceptibility: The first replication study in the Brazilian population.
Authors: Israel Gomy, Erika Maria Monteiro Santos, Graziela Machado Gruner Turco Spilborghs, Sandra Regina de Araujo da Silva Viola, Samuel Aguiar, Dirce Maria Carraro, Silvia Regina Rogatto, Luis Carvajal-Carmona, Benedito Mauro Rossi
Journal: Journal of Clinical Oncology (2013)

361 Background: Inherited susceptibility to colorectal cancer (CRC) is known since twin studies have revealed 35% of heritability. Genome-wide association studies (GWAS) have uncovered less than a half of this proportion through genotyping tagSNPs of individuals with European ancestry. To date only 20 common SNPs have achieved genome-wide significance and replication studies from non-European populations are scarce. Here we show preliminary data of the first study of CRC inherited susceptibility in the Brazilian population and aimed to replicate European studies. Methods: We genotyped 1,395 individuals (675 cases and 720 controls) for 10 tagSNPs (rs6983267, rs4939827, rs4779584, rs16892766, rs10795668, rs4444235, rs9929218, rs10411210, rs961253, rs3802842) using TaqMan SNP Genotyping Assays and SDS2.3 software (Applied Biosystems). We exclude from the analysis SNPs with significant deviation from Hardy-Weinberg equilibrium. Results: Significant association was found between six out of ten SNPs and CRC risk for most genetic models. One SNP (rs10411210) was associated with a low risk of CRC. Conclusions: Despite we did not analyze population stratification, this study partially replicate European GWAS in an admixed population. Therefore, it is worth to explore other ethnic backgrounds that would ultimately help to uncover the missing heritability of CRC and narrow the boundaries of the genetic architecture of CRC susceptibility. [Table: see text]
Patient (Pt) and caregiver (Cg) perspectives in non-small cell lung cancer (NSCLC).
Authors: Corey J. Langer, Tracey L. Evans, Chandra Prakash Belani, Gary William Middleton, Christos Chouaid, Kathleen Pearson, Daniel E. Ball, Elizabeth N. Bush, Susan C. Guba, Johan F. Vansteenkiste
Journal: Journal of Clinical Oncology (2012)

4 Background: Research investigating Pts’ preferences in treatment (tx) decisions for advanced (NSCLC) has generally been limited to smaller, single-country studies or anecdotal reports, and has rarely included Cgs’ perspectives. Methods: A 30 minute online or phone survey was conducted 28 June to 9 August, 2011. Survey participants (SP) included NSCLC Pts (n=245) or Cgs of NSCLC Pts (n=251) treated in the prior 12 months. A 1:1 non-paired sample of Pts and Cgs was sought in the US (n=295), France (FR; n= 100) and Germany (DE; n=101). FR and DE data were weighted to better reflect the age distribution of NSCLC in those countries, then combined. Results: For NSCLC SP, 64% were ≤65 years; 52% were male; 13% current smokers; 64% former smokers. Disease was localized in 21%, advanced in 73% and unknown in 6%. Tx was ongoing in 54%, and in 15% and 31% respectively tx was completed &lt; 3 or 3-12 months previously. SPs elected tx to maintain independence (90%) and to control the cancer (89%); 81% were willing to continue tx indefinitely to maintain disease control. Although 69% of SP were greatly concerned about chemotherapy side effects, 60% were willing to endure significant side effects to live longer. SPs were comfortable asking their doctor questions (84%), and 68% were comfortable asking questions if they disagreed with recommended tx; 58% of SPs usually deferred tx decisions to the doctor. Comprehension of the tx plan was higher upon tx initiation (71%) than at diagnosis (46%) or at time of initial explanation by the doctor (62%). Many SPs (77%) relied on the nurses to help them understand their condition/tx. Among SPs in whom tx was discontinued (n=230), the most common reported reasons for stopping were that the cancer decreased in size (41%) or had stopped growing (28%). Only 14% believed tx was stopped because the cancer was not responsive, while 13% believed the cancer was gone. Conclusions: This large 3-country survey characterized factors important to the NSCLC SP in determining motivations for tx including a desire to control the disease and willingness to continue treatment for disease control if there was an acceptable risk/benefit balance. The survey also indicated a possible misapprehension on the reason(s) tx was halted.
Clinical outcomes in patients age 40 or younger at diagnosis of synchronous metastatic colorectal cancer: A 20-year experience at Memorial Sloan-Kettering Cancer Center.
Authors: M. A. Lowery, D. J. Gallagher, M. Capanu, J. F. Chou, N. E. Kemeny
Journal: Journal of Clinical Oncology (2011)

e14050 Background: The incidence of rectal cancer in patients under 40 years is increasing; however, the impact of age ≤40 at diagnosis of CRC on outcome is unclear. We reviewed the records of young adults diagnosed with metastatic CRC at our institution over a 20-year period to assess the impact of demographic, pathologic and treatment related variables on clinical outcomes. Methods: Approval was obtained from the Institutional Review Board. 301 patients diagnosed with synchronous metastatic CRC age ≤ 40 years from Jan 1991 to Jan 2011 were identified from the institutional database. Overall survival (OS) was calculated from the date of cytological or pathological confirmation of diagnosis to date of death or last follow-up, and was calculated using the Kaplan-Meier method. Results: Median OS was 2 years. Factors associated with improved survival included liver limited disease, resection of hepatic metastases and use of hepatic arterial chemotherapy. Patients with a known history of Crohn's disease or ulcerative colitis and those with African American or Asian ethnicity had significantly reduced survival. KRAS mutation was identified in 19 of 55 patients (35%). Conclusions: In this retrospective analysis, mOS of young patients with metastatic CRC at diagnosis is similar to that expected in an unselected population. Patients who underwent resection of hepatic metastases had significantly better survival, reflecting the small but significant cure rate of patients rendered disease free by hepatic metastatectomy. Characteristics HR 95% CI P Male vs. female 0.977 (0.756-1.262) 0.8561 Race 0.0184 Asian vs. White 1.231 (0.727-2.086) Black vs. White 1.782 (1.187-2.675) IBD yes vs no 2.275 (1.269-4.079) 0.0058 Pregnant yes vs no 1.037 (0.604-1.782) 0.8945 Liver only disease 0.577 (0.446-0.747) <0.001 Liver resection 0.290 (0.209-0.401) <0.0001 HAI chemotherapy 0.631 (0.456-0.874) 0.0056
Assessment of the effect of ethnicity on linifanib tolerability and pharmacokinetics in patients with cancer.
Authors: J. Xiong, Y. Chiu, R. S. Pradhan, X. Li, X. Li, D. M. Carlson, W. Awni
Journal: Journal of Clinical Oncology (2011)

e13082 Background: Linifanib is a novel orally active, potent and selective vascular endothelial growth factor receptor and platelet derived growth factor receptor kinase inhibitor. Linifanib activity as a monotherapy has been demonstrated in phase 1 and 2 trials in patients with a variety of advanced solid tumors. The aim of this assessment was to evaluate the impact of ethnicity on linifanib tolerability and pharmacokinetics (PK) in cancer patients. Methods: Linifanib tolerability and PK were compared across Chinese, Japanese and non-Asian cancer patients from 8 clinical trials. Data for the Chinese and Japanese analyses were obtained from 2 phase 1 and 3 phase 2 trials, and 3 phase 1, one phase 2, and one phase 3 trial, respectively. The impact of ethnicity on tolerability was assessed by evaluating significance of ethnicity on the exposure-safety relationship. Logistic regression analysis was conducted to construct the exposure-safety relationship for eight common adverse events (hypertension, asthenia, GI-abdominal disorder, diarrhea, skin toxicity 1, skin toxicity 2, proteinuria and anorexia). The steady-state linifanib PK exposure parameters, when not available from non-compartmental analysis, were estimated modeling the available phase 1 and 2 data using a population PK approach. Results: The exposure-safety response analysis showed that ethnicity was not a significant factor influencing the exposure-safety response relationship for any of the tested adverse events. In addition, linifanib exposures as dose-normalized (DN) AUC were similar between Chinese and non-Chinese patients (DN AUC: 0.36 ± 0.16 (N=106) and 0.32 ± 0.16 (N=160), respectively) and between Japanese and non-Japanese patients (DN AUC: 0.34 ± 0.11 [N=11] and 0.34 ± 0.15 [N=36), respectively). Conclusions: There appears to be no meaningful ethnic differences in linifanib tolerability and PK across Chinese, Japanese and non-Asian cancer patients.
Sex, income and age-related differences in colorectal cancer care: results from the Project for an Ontario Women's Health Evidence-based Report Card (POWER) study
Authors: M. K. Krzyzanowska, L. Barbera, L. Elit, D. Hodgson, A. Razzaq, R. Saskin, D. Urbach, A. Bierman
Journal: Journal of Clinical Oncology (2008)

6509 Background: The goal of the POWER study is to improve health and reduce inequities among women of Ontario using performance measurement. Indicators are selected to facilitate assessment of care by sex and socioeconomic status (SES). Results pertaining to colorectal cancer (CRC) are presented. Methods: An expert panel process was used to identify performance measures spanning disease spectrum from screening through follow-up care and feasible to be evaluated from administrative data. The most recently available data (2003–2005) from Ontario Cancer Registry, Registered Persons Database as well as provincial billing and hospital databases were then used to evaluate the selected measures stratified by age, sex, and income. Results: Eight indicators relevant to CRC were selected by the panel, the majority of which related to processes of care. Except for higher incidence of CRC in men as compared to women (83 v. 67/100,000) and lower rates of referral to radiation oncologist after surgery among women with rectal cancer (48.7 v. 55.8%), there were no appreciable differences in care by sex for the other 6 indicators. These indicators included 5-year survival, screening using fecal occult blood testing (FOBT), time to surgery, rates of sphincter preserving procedures, referral to medical oncology and follow-up care. In contrast, lower SES was associated with lower rates of FOBT screening (12.0 v. 17.0% in lowest [Q1] v. highest [Q5] quintiles, respectively), worse 5-year survival (46.4 v. 55.1%, Q1/Q5) and lower rates of follow-up colonoscopy within 24 months after diagnosis (77.9 v. 84.4%, Q1/Q5). Low income men appeared to be especially disadvantaged with highest incidence of CRC (92/100,000) and lowest 5-year survival (42.1%). Trends towards less care were also seen with increasing age in referral rates to medical and radiation oncology and follow-up colonoscopy but not in time to or type of surgery. Conclusions: Income and age-related rather than sex differences exist in processes of care for CRC with lower performance among low SES groups and the elderly. Further work is necessary to determine how these differences in processes of care affect outcomes and ways to facilitate access to care by disadvantaged groups. No significant financial relationships to disclose.
Do the Safety and Efficacy Outcomes Reported in the Clinical Trials of Direct Oral Anticoagulants (DOAC) Translate to the Real-World?
Authors: Shammim Haji, Jignesh P Patel, Vivian Auyeung, Lara N Roberts, Julia Czuprynska, Raj K Patel, Roopen Arya
Journal: Blood (2015)
Clinical benefits of bevacizumab in metastatic colorectal cancer depending on KRAS status.
Authors: Keisuke Kurimoto, Kiyoshi Ishigure, Yoshiyasu Kato, Yasuyuki Asai, Nobutake Tanaka, Song Ryo, Hidenobu Matsushita, Junichi Tobinaga, Ryuichi Fukuyama, Hiruhumi Kuroda, Tomoo Fujii
Journal: Journal of Clinical Oncology (2014)

636 Background: KRAS status is the therapeutic marker of anti-EGFR drug, and may be the prognostic marker of metastatic colorectal cancer (mCRC). However, there is no consensus whether bevacizumab (anti-VEGF drug) benefits patients with mutated KRAS in mCRC. We investigated the clinical benefits of bevacizumab treatment in mCRC depending on KRAS status, retrospectively. Methods: We investigated 49 patients who received chemotherapies with bevacizumab as first-line treatment for mCRC from May 2008 through June 2013. We evaluated response rate (RR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tumor reduction rate and the adverse events (CTCAE v4.0 - JCOG) depending on KRAS status. Results: The median age of the patients was 66 years (range; 36 - 80). Forty-five patients received oxaliplatin-based chemotherapies with bevacizumab and four patients received irinotecan-based chemotherapies with bevacizumab. KRAS status of 30 patients was wild type and that of 19 patients was mutation type. There was no difference in patient characteristics between KRAS wild type (WT) and mutation type (MT). In all 49 patients, RR was 62.5%. DCR was 91.7%. The median PFS was 10.9 months. In RR, patients with KRAS wild type tumors had better outcome than patients with mutant type tumors (WT : MT, 69.0% : 52.6%, no statistically difference). A similar tendency was seen in DCR (WT : MT, 96.6% : 84.2%, no statistically difference). The average reduction rate in KRAS WT was 42.7% and in KRAS MT was 32.3% (p = 0.309). In the KRAS wild patients, the median PFS was longer than that in the KRAS mutant patients (WT : MT, 11.8 : 8.9 months, Log Rank p = 0.583), but there is no statistically difference between two groups. In median OS, there was no difference between two groups (WT : MT, 21.0 : 20.8 months, Log Rank p = 0.393). The incidence of severe adverse events was not statistically different between KRAS WT group and MT group. Conclusions: Regardless of KRAS status, bevacizumab provides clinical benefits for patients with mCRC.
Low-dose thalidomide and interferon alpha-2b in patients with metastatic melanoma: The final results of a pilot study
Authors: H. R. Schlossberg, M. Solti, D. Berd, M. J. Mastrangelo, T. Sato
Journal: Journal of Clinical Oncology (2005)

7571 Background Melanoma is a hypervascular tumor and angiogenesis plays a critical role in the development/progression of metastases. Since various pathways are involved in tumor angiogenesis, a combination of agents with different anti-angiogenesis activities is a reasonable approach. Methods Patients with stage IV melanoma who failed first-line treatments were treated with a combination of thalidomide [Celgene, Warren, NJ] (200 mg/day, p.o.) and interferon alpha-2b (3 MIU, 3x/week, s.c.). Patients were evaluated monthly for toxicity and every 2 months for clinical response. Stabilization or regression of metastases was the primary endpoint of the study. Overall survival (OS), progression free survival (PFS), time to progression (TTP) and toxicity were also evaluated as secondary endpoints. Results Fifteen patients were enrolled: 9 cutaneous, 6 uveal melanoma; 10 males, 5 females; median age, 56.7 years (42–70). One patient with adrenal, mediastinal and skin metastases achieved partial response (PR), 3 patients achieved stable disease (SD), and 9 patients progressed. Two patients were not evaluable due to discontinuation of treatment prior to initial evaluation for response at 2 month (neurotoxicity, n=1; withdrawal of consent, n=1). The overall response rates (PR+SD) of “intent to treat” patients and evaluable patients were 26.7% and 30.8%, respectively. TTP was 8 months for the patient with PR, and 4, 5.5 and 12 months for 3 patients with SD. With the median follow-up of 22.8 months (12–32 months), the median OS and PFS of “intent to treat” patients were 4.2 months (1–32 months) and 3.4 months (0.5–14 months), respectively. Grade 3 toxicities related to treatment included neutropenia (n=5), elevation of transaminases (n=2), and neuropathy (n=1). No treatment-related deaths were experienced. Conclusions These preliminary results suggest that combination treatment with thalidomide and interferon alpha would be an effective palliative treatment for previously treated, stage IV melanoma patients. No significant financial relationships to disclose.
A home-based palliative care pilot program for patients with advanced cancer.
Authors: Rae Seitz, Charles F. Miller, Michael Duick, Robert Eubanks
Journal: Journal of Clinical Oncology (2015)

164 Background: Advanced cancer care often lacks a comprehensive approach; in Hawaii most oncology practices do not have access to palliative care teams. This causes high use of acute care services and suboptimal symptom management. Hawaii Medical Service Association (HMSA) created a pilot program called Supportive Care in which home-based palliative care services are offered to members with advanced cancer with goals of improved clinical outcomes and decrease utilization of acute care services Methods: Patients must have stage III or IV malignancy and ECOG PS of 2 or greater. Palliative care services are provided by Medicare-certified hospice agencies, with interdisciplinary teams, 24/7 on-call capacity, and expertise in symptom management. Hospice agencies are paid by HMSA to provide intermittent home visits. DME and pharmaceuticals. Care is coordinated with the patient's treating oncologist and other care providers. Each patient may receive 90 days of Supportive Care services in a 12 month period. Services are suspended during hospitalization or placement in a skilled nursing facility. Results: Patients enrolled in this program utilized hospital services significantly less than other Medicare Beneficiaries during the end-of-life period, suggesting that complex medical and psychosocial needs can be met in the home environment. The table compares findings from cancer patients enrolled in Supportive Care during 2014 with the most recent data available from The Dartmouth Atlas of Health Care. Conclusions: Multiple studies show improved quality of life for cancer patients receiving palliative care. Supportive Care resulted in improved clinical outcomes. Anecdotal feedback indicates high satisfaction among patients, families, and providers. Research to collect data and quantify satisfaction continues. [Table: see text]
Your opinion counts: How do you treat atypical/suspicious cytology?
Authors: Thomas Andrew Longo, Ajay Gopalakrishna, Joseph J Fantony, Brant Allen Inman
Journal: Journal of Clinical Oncology (2016)

463 Background: Urine cytology has often been reported as a highly specific but poorly sensitive test. Cytology is reported as positive, negative, atypical, or suspicious. Atypical/suspicious cytologies account for roughly a quarter of the results and present a clinical dilemma. Physicians’ risk aversion means they are typically treated as positive and result in clinical action. We test the effects of this assumption on sensitivity and specificity. Methods: After IRB approval, we queried clinical and pathology databases to identify all subjects at Duke University Medical Center who had undergone both a urine cytology and a cystoscopy from 1/2003 to 1/2012. Diagnostic test performance metrics were calculated using logistic models: (a) a generalized estimating equation (GEE) and (b) a generalized linear mixed model (GLMM). These take into account clustered/correlated test results that occur due to repeated testing within subjects. Results: A total of 990 unique subjects were identified that provided 4,733 pairs of cytology and cystoscopy for analysis. Our cohort was 61% male, 75% Caucasian, and had 54% current or former smokers. Of cytologies, 1898 (40%) were negative, 423 (9%) positive, and 2408 (51%) suspicious or atypical. When suspicious/atypical cytology results using the GLMM model were classified as positive, the specificity was 62% [95%CI: 58-66%] and the sensitivity was 41% [95% CI: 38-44%]. When these results were re-classified as negative, this had the effect of a large increase in specificity 100% [95%CI: 100-100%] with a consequent decrease in sensitivity 0% [95%CI: 0-2%]. Conclusions: In our study, the performance of urine cytology depended heavily on how the equivocal (atypical/suspicious) results were classified and dealt with. Our sensitivity was maximized when equivocal cytologies were considered positive, but at significant detriment of the specificity. Contrarily, our specificity improved greatly when the equivocal results were considered negative, but at the expense of a poor sensitivity. Furthermore, the diagnosis of an atypical/suspicious cytology was higher at our medical center than reported in the literature, and therefore significantly overestimated the performance of the urine cytology test.
Collaborative care with behavioural activation cuts depressive symptoms in older people, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Collaborative care allowing older people with subclinical depression access to behavioural activation reduced depressive symptoms more than standard care in a randomised trial in UK general practice.1

Depression is common in older people, as figures show that it may affect one in seven people over 65. But limited evidence exists on effective treatment strategies in older people with mild depressive disorders …
Biological and clinical effects of single agent treatment with atorvastatin in patients with non-Hodgkin’s lymphoma
Authors: A. C. Fan, M. Orban, H. E. Lee, A. E. Shirer, R. Rajwanshi, C. Kong, Y. Natkunam, S. Coutre, D. W. Felsher
Journal: Journal of Clinical Oncology (2008)

8529 Background: Statins have been suggested to have potential therapeutic effects against cancers. Recently, we reported that atorvastatin can reverse and prevent tumorigenesis in a transgenic mouse model of lymphoma. Since many of our patients being treated for cancer are taking statins, it is important to know if these agents have effects on tumor bioactivity. We designed a phase II study in patients with non-Hodgkin’s lymphoma to measure changes in tumor bioactivity and clinical response upon atorvastatin administration. Methods: Patients were eligible if they had low grade or refractory NHL, adequate organ function, and had not taken statins in the prior 6 months. Patients received 80 mg atorvastatin daily and underwent tumor sampling on days 1 and 8. Patients were restaged every 3 months beginning day 43 and continued on study if they achieved a clinical PR or CR at each re-evaluation for up to 12 months. The primary endpoint was to measure change in tumor bioactivity, defined as either a 50% increase in tumor apoptosis measured by flow cytometry on treatment day 8 compared with baseline on day 1, or a 50% change in phosphorylated oncogene expression on day 8 compared with day 1. A secondary endpoint was to evaluate clinical efficacy. Enrollment goal was 14 patients. Results: To date 12 of an intended 14 patients have been enrolled. The primary endpoint of greater than 50% increase in apoptosis was observed in 8 of 12 patients. In 8 patients, there was a mean increase in apoptosis by 260% on day 8. To account for these biologic effects, we observed discrete changes in the phosphorylation state of oncoproteins including MAPK/p38 and phospholipase C in response to atorvastatin treatment. Notably, one clinical PR was documented in a patient whose response included a 30% decrease in tumor measurement on CT scan and a corresponding 32% decrease in circulating tumor cells. In addition, 4 patients with CLL showed an 18–37% decrease in circulating WBCs. Conclusions: Single agent atorvastatin has a measurable effect on tumor bioactivity in patients with lymphoma and is worthy of further investigation. Our results suggest that investigators should be aware that statins appear to induce significant biological and in some cases clinical effects on patients with cancer. No significant financial relationships to disclose.